Search results for: therapeutic exercises

Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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Authors: Prashantkumar Waghe, N. Prakash, N. D. Prasada, L. V. Lokesh, M. Vijay Kumar, Vinay Tikare

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Arsenic is a naturally occurring metalloid with potent toxic effects. It is ubiquitous in the environment and released from both natural and anthropogenic sources. It has the potential to cause various health hazards in exposed populations. Arsenic exposure through drinking water is considered as one of the most serious global environmental threats including Southeast Asia. The aim of present study was to evaluate the modulatory role of subacute exposure to sodium (meta) arsenite on the antinociceptive, anti-inflammatory and antipyretic responses mediated by meloxicam in rats. Rats were exposed to arsenic as sodium arsenite through drinking water for 28 days. A single dose of meloxicam (2 mg/kg b. wt.) was administered by oral gavage on the 29th day. The exact time of meloxicam administration depended on the type of test. Rats were divided randomly into 5 groups (n=6). Group I served as normal control and received arsenic free drinking water, while rats in group II were maintained similar to Group I but received meloxicam on 29th day. Groups III, IV and V were pre-exposed to arsenic through drinking water at 0.5, 5.0 and 50 ppm, respectively, for 28 days and was administered meloxicam next day and; pain and inflammation carried out by using formalin-induced nociception and carrageenan-induced inflammatory model(s), respectively by using standard protocol. For assessment of antipyretic effects, one more additional group (Group VI) was taken and given LPS @ 1.8 mg/kg b. wt. for induction of pyrexia (LPS control). Higher dose of arsenic inhibited the meloxicam mediated antinociceptive, anti-inflammatory and antipyretic responses. Further, meloxicam inhibited the arsenic induced level of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 and COX2 mediated prostaglandin E2 in hind paw muscle. These results suggest a functional antagonism of meloxicam by arsenic. This may relate to arsenic mediated local release of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 releases COX2 mediated prostaglandin E2. Based on the experimental study, it is concluded that sub-acute exposure to arsenic through drinking water aggravate pyrexia, inflammation and pain at environment relevant concentration and decrease the therapeutic efficacy of meloxicam at higher level of arsenite exposure. Thus, the observation made has clinical relevance in situations where animals are exposed to arsenite epidemic geographical locations.

Keywords: arsenic, analgesic activity, meloxicam, Wistar rats

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Authors: Udeshika Yapa Bandara, Chamindri Witharana, Preethi Soysa

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Pomegranate fruits are used in cancer treatment in Ayurveda, Sri Lanka. Due to prevailing therapeutic effects of phytochemicals, this study was focus on anti-cancer properties of the constituents in the parts of Pomegranate fruit. Furthermore, the method of extraction, plays a crucial step of the phytochemical analysis. Therefore, this study was focus on different extraction methods. Five techniques were involved for the peel and the pericarp to evaluate the most effective extraction method; Boiling with electric burner (BL), Sonication (SN), Microwaving (MC), Heating in a 50°C water bath (WB) and Sonication followed by Microwaving (SN-MC). The presence of polyphenolic and flavonoid contents were evaluated to recognize the best extraction method for polyphenols. The total phenolic content was measured spectrophotometrically by Folin-Ciocalteu method and expressed as Gallic Acid Equivalents (w/w% GAE). Total flavonoid content was also determined spectrophotometrically with Aluminium chloride colourimetric assay and expressed as Quercetin Equivalents (w/w % QE). Pomegranate juice was taken as fermented juice (with Saccharomyces bayanus) and fresh juice. Powdered seeds were refluxed, filtered and freeze-dried. 2g of freeze-dried powder of each component was dissolved in 100ml of De-ionized water for extraction. For the comparison of antioxidant activity and total phenol content, the polyphenols were removed by the Polyvinylpolypyrrolidone (PVVP) column and fermented and fresh juice were tested for the 1, 1-diphenyl-2-picrylhydrazil (DPPH) radical scavenging activity, before and after the removal of polyphenols. For the peel samples of Pomegranate fruit, total phenol and flavonoid contents were high in Sonication (SN). In pericarp, total phenol and flavonoid contents were highly exhibited in method of Sonication (SN). A significant difference was observed (P< 0.05) in total phenol and flavonoid contents, between five extraction methods for both peel and pericarp samples. Fermented juice had a greatest polyphenolic and flavonoid contents comparative to fresh juice. After removing polyphenols of fermented juice and fresh juice using Polyvinyl polypyrrolidone (PVVP) column, low antioxidant activity was resulted for DPPH antioxidant activity assay. Seeds had a very low total phenol and flavonoid contents according to the results. Although, Pomegranate peel is the main waste component of the fruit, it has an excellent polyphenolic and flavonoid contents compared to other parts of the fruit, devoid of the method of extraction. Polyphenols play a major role for antioxidant activity.

Keywords: antioxidant activity, flavonoids, polyphenols, pomegranate

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Authors: Daifeng Hao, Guang Feng, Jingfeng Zhao, Tao Li, Xiaoye Tuo

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Objective: To retrospectively analyze the clinical characteristics of incision infection with sternal osteomyelitis sinus tract after cardiac surgery and the operation method and therapeutic effect of filling and repairing with activated PRP gel. Methods: From March 2011 to October 2022, 142 cases of incision infection after cardiac surgery with sternal osteomyelitis sinus were retrospectively analyzed, and the causes of poor wound healing after surgery, wound characteristics, perioperative wound management were summarized. Treatment during operation, collection and storage process of autologous PRP before debridement surgery, PRP filling repair and activation method after debridement surgery, effect of anticoagulant drugs on surgery, postoperative complications and average wound healing time, etc.. Results: Among the cases in this group, 53.3% underwent coronary artery bypass grafting, 36.8% underwent artificial heart valve replacement, 8.2% underwent aortic artificial vessel replacement, and 1.7% underwent allogeneic heart transplantation. The main causes of poor incision healing were suture reaction, fat liquefaction, osteoporosis, diabetes, and metal allergy in sequence. The wound is characterized by an infected sinus tract. Before the operation, 100-150ml of PRP with 4 times the physiological concentration was collected separately with a blood component separation device. After sinus debridement, PRP was perfused to fill the bony defect in the middle of the sternum, activated with thrombin freeze-dried powder and calcium gluconate injection to form a gel, and the outer skin and subcutaneous tissue were sutured freely. 62.9% of patients discontinued warfarin during the perioperative period, and 37.1% of patients maintained warfarin treatment. There was no significant difference in the incidence of postoperative wound hematoma. The average postoperative wound healing time was 12.9±4.7 days, and there was no obvious postoperative complication. Conclusions: Application of activated PRP gel to fill incision infection with sternal osteomyelitis sinus after cardiac surgery has a less surgical injury and satisfactory and stable curative effect. It can completely replace the previously used pectoralis major muscle flap transplantation operation scheme.

Keywords: platelet-rich plasma, negative-pressure wound therapy, sternal osteomyelitis, cardiac surgery

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Authors: Takuya Suzuki, Atsushi Shirai, Takashi Seki

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Acupuncture therapy is one of the treatments in traditional Chinese medicine. Recently, some reports have shown the effectiveness of acupuncture. However, its full acceptance has been hindered by the lack of understanding on mechanism of the therapy. Acupuncture applied to Zusanli (ST-36) enhances blood flow volume in superior mesenteric artery (SMA), yielding peripheral vascular resistance – regulated blood flow of SMA dominated by the parasympathetic system and inhibition of sympathetic system. In this study, a lumped-parameter approximation model of blood flow in the systemic arteries was developed. This model was extremely simple, consisting of the aorta, carotid arteries, arteries of the four limbs and SMA, and their peripheral vascular resistances. Here, the individual artery was simplified to a tapered tube and the resistances were modelled by a linear resistance. We numerically investigated contribution of the peripheral vascular resistance of SMA to the systemic blood distribution using this model. In addition to the upstream end of the model, which correlates with the left ventricle, two types of boundary condition were applied; mean left ventricular pressure which correlates with blood pressure (BP) and mean cardiac output which corresponds to cardiac index (CI). We examined it to reproduce the experimentally obtained hemodynamic change, in terms of the ratio of the aforementioned hemodynamic parameters from their initial values before the acupuncture, by regulating the peripheral vascular resistances and the upstream boundary condition. First, only the peripheral vascular resistance of SMA was changed to show contribution of the resistance to the change in blood flow volume in SMA, expecting reproduction of the experimentally obtained change. It was found, however, this was not enough to reproduce the experimental result. Then, we also changed the resistances of the other arteries together with the value given at upstream boundary. Here, the resistances of the other arteries were changed simultaneously in the same amount. Consequently, we successfully reproduced the hemodynamic change to find that regulation of the upstream boundary condition to the value experimentally obtained after the stimulation is necessary for the reproduction, though statistically significant changes in BP and CI were not observed in the experiment. It is generally known that sympathetic and parasympathetic tones take part in regulation of whole the systemic circulation including the cardiac function. The present result indicates that stimulation to ST-36 could induce vasodilation of peripheral circulation of SMA and vasoconstriction of that of other arteries. In addition, it implies that experimentally obtained small changes in BP and CI induced by the acupuncture may be involved in the therapeutic response.

Keywords: acupuncture, hemodynamics, lumped-parameter approximation, modeling, systemic vascular resistance

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Authors: Nishanth Venugopal Menon, Chuah Yon Jin, Samantha Phey, Wu Yingnan, Zhang Ying, Vincent Chan, Kang Yuejun

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Cell Migration is a vital phenomenon that the cells undergo in various physiological processes like wound healing, disease progression, embryogenesis, etc. Cell migration depends primarily on the chemical and physical cues available in the cellular environment. The chemical cue involves the chemokines secreted and gradients generated in the environment while physical cues indicate the impact of matrix properties like nanotopography and stiffness on the cells. Mesenchymal Stem Cells (MSCs) have been shown to have a role wound healing in vivo and its migration to the site of the wound has been shown to have a therapeutic effect. In the field of stem cell based tissue regeneration of bones and cartilage, one approach has been to introduce scaffold laden with MSCs into the site of injury to enable tissue regeneration. In this work, we have studied the combinatorial impact of the substrate physical properties on MSC migration. A microfluidic in vitro model was created to perform the migration studies. The microfluidic model used is a three compartment device consisting of two cell seeding compartments and one migration compartment. Four different PDMS substrates with varying substrate roughness, stiffness and hydrophobicity were created. Its surface roughness and stiffness was measured using Atomic Force Microscopy (AFM) while its hydrphobicity was measured from the water contact angle using an optical tensiometer. These PDMS substrates are sealed to the microfluidic chip following which the MSCs are seeded and the cell migration is studied over the period of a week. Cell migration was quantified using fluorescence imaging of the cytoskeleton (F-actin) to find out the area covered by the cells inside the migration compartment. The impact of adhesion proteins on cell migration was also quantified using a real-time polymerase chain reaction (qRT PCR). These results suggested that the optimal substrate for cell migration would be one with an intermediate level of roughness, stiffness and hydrophobicity. A higher or lower value of these properties affected cell migration negatively. These observations have helped us in understanding that different substrate properties need to be considered in tandem, especially while designing scaffolds for tissue regeneration as cell migration is normally impacted by the combinatorial impact of the matrix. These observations may lead us to scaffold optimization in future tissue regeneration applications.

Keywords: cell migration, microfluidics, in vitro model, stem cell migration, scaffold, substrate properties

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Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Spondylothoracic dysostosis, also known as Jarcho-Levin syndrome, is defined by a shortened neck and thorax, a protruding abdomen, inguinal and umbilical hernias, atypical spinal structure and rib fusion, leading to restricted chest movement or difficulty in breathing, along with urinary tract abnormalities and, potentially severe scoliosis. Aim: This is the case of a patient diagnosed with Jarcho-Levin syndrome, aiming to detail the range of abnormalities observed in this syndrome, the observed complications, and the therapeutic approaches employed. Results: A three-month-old male infant, born of a consanguineous marriage, delivered at full term by cesarean section, was admitted to the pediatric department for severe acute bronchiolitis. In his prenatal history, morphological ultrasound revealed macrosomia, a shortened spine, irregular vertebrae with thickened skin, normal fetal cardiac ultrasound, and the absence of the right kidney. His perinatal history included respiratory distress, requiring ventilatory support for five days. Upon physical examination, he had stunted growth, scoliosis, a short neck and trunk, longer upper limbs compared to lower limbs, varus equinus in the right foot, a neural tube defect, a low hairline, and low-set ears. Spondylothoracic dysostosis was suspected, leading to further investigations, including a normal transfontaneous ultrasound, a spinal cord ultrasound revealing a lipomyelocele-type closed dysraphism with a low-attached cord, an abdominal ultrasound indicating a single left kidney, and a cardiac ultrasound identifying Kommerell syndrome. Due to a lack of resources, genetic testing could not be performed, and the diagnosis was based on clinical criteria. Conclusion: Jarcho-Levin syndrome can result in a mortality rate of about 50%, primarily due to respiratory complications associated with thoracic insufficiency syndrome. Other complications, like heart and neural tube defects, can also lead to premature mortality. Therefore, early diagnosis and comprehensive treatment involving various specialists are essential.

Keywords: Jarcho-Levin syndrome, congenital disorder, scoliosis, spondylothoracic dysostosis, neural tube defect

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Authors: Akulov M. A., Orlova O. R., Zaharov V. O., Tomskij A. A.

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Introduction: One of the common postoperative complications of posterior cranial fossa (PCF) and cerebello-pontine angle tumor treatment is a facial nerve palsy, which leads to multiple and resistant to treatment impairments of mimic muscles structure and functions. After 4-6 months after facial nerve palsy with insufficient therapeutic intervention patients develop a postparalythic syndrome, which includes such symptoms as mimic muscle insufficiency, mimic muscle contractures, synkinesis and spontaneous muscular twitching. A novel method of treatment is the use of a recent local neuromuscular blocking agent– botulinum toxin A (BTA). Experience of BTA treatment enables an assumption that it can be successfully used in late facial nerve palsy complications to significantly increase quality of life of patients. Study aim. To evaluate the efficacy of botulinum toxin A (BTA) (Xeomin) treatment in patients with late facial nerve palsy complications. Patients and Methods: 31 patients aged 27-59 years 6 months after facial nerve palsy development were evaluated. All patients received conventional treatment, including massage, movement therapy etc. Facial nerve palsy developed after acoustic nerve tumor resection in 23 (74,2%) patients, petroclival meningioma resection – in 8 (25,8%) patients. The first group included 17 (54,8%) patients, receiving BT-therapy; the second group – 14 (45,2%) patients continuing conventional treatment. BT-injections were performed in synkinesis or contracture points 1-2 U on injured site and 2-4 U on healthy side (for symmetry). Facial nerve function was evaluated on 2 and 4 months of therapy according to House-Brackman scale. Pain syndrome alleviation was assessed on VAS. Results: At baseline all patients in the first and second groups demonstrated аpostparalytic syndrome. We observed a significant improvement in patients receiving BTA after only one month of treatment. Mean VAS score at baseline was 80,4±18,7 and 77,9±18,2 in the first and second group, respectively. In the first group after one month of treatment we observed a significant decrease of pain syndrome – mean VAS score was 44,7±10,2 (р<0,01), whereas in the second group VAS score was as high as 61,8±9,4 points (p>0,05). By the 3d month of treatment pain syndrome intensity continued to decrease in both groups, but, the first group demonstrated significantly better results; mean score was 8,2±3,1 and 31,8±4,6 in the first and second group, respectively (р<0,01). Total House-Brackman score at baseline was 3,67±0,16 in the first group and 3,74±0,19 in the second group. Treatment resulted in a significant symptom improvement in the first group, with no improvement in the second group. After 4 months of treatment House-Brockman score in the first group was 3,1-fold lower, than in the second group (р<0,05). Conclusion: Botulinum toxin injections decrease postparalytic syndrome symptoms in patients with facial nerve palsy.

Keywords: botulinum toxin, facial nerve palsy, postparalytic syndrome, synkinesis

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Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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Authors: Sandra Adarve, Jhon Osorio

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Uncertainty has been studied in patients with different types of cancer, except in patients with hematologic cancer and undergoing transplantation. The purpose of this study was to identify factors associated with uncertainty in adults patients with malignant hemato-oncology diseases who are scheduled to undergo hematopoietic stem cell transplantation based on Merle Mishel´s Uncertainty theory. This was a cross-sectional study with an analytical purpose. The study sample included 50 patients with leukemia, myeloma, and lymphoma selected by non-probability sampling by convenience and intention. Sociodemographic and clinical variables were measured. Mishel´s Scale of Uncertainty in Illness was used for the measurement of uncertainty. A bivariate and multivariate analyses were performed to explore the relationships and associations between the different variables and uncertainty level. For this analysis, the distribution of the uncertainty scale values was evaluated through the Shapiro-Wilk normality test to identify statistical tests to be used. A multivariate analysis was conducted through a logistic regression using step-by-step technique. Patients were 18-74 years old, with a mean age of 44.8. Over time, the disease course had a median of 9.5 months, an opportunity was found in the performance of the transplantation of < 20 days for 50% of the patients. Regarding the uncertainty scale, a mean score of 95.46 was identified. When the dimensions of the scale were analyzed, the mean score of the framework of stimuli was 25.6, of cognitive ability was 47.4 and structure providers was 22.8. Age was identified to correlate with the total uncertainty score (p=0.012). Additionally, a statistically significant difference was evidenced between different religious creeds and uncertainty score (p=0.023), education level (p=0.012), family history of cancer (p=0.001), the presence of comorbidities (p=0.023) and previous radiotherapy treatment (p=0.022). After performing logistic regression, previous radiotherapy treatment (OR=0.04 IC95% (0.004-0.48)) and family history of cancer (OR=30.7 IC95% (2.7-349)) were found to be factors associated with the high level of uncertainty. Uncertainty is present in high levels in patients who are going to be subjected to bone marrow transplantation, and it is the responsibility of the nurse to assess the levels of uncertainty and the presence of factors that may contribute to their presence. Once it has been valued, the uncertainty must be intervened from the identified associated factors, especially all those that have to do with the cognitive capacity. This implies the implementation and design of intervention strategies to improve the knowledge related to the disease and the therapeutic procedures to which the patients will be subjected. All interventions should favor the adaptation of these patients to their current experience and contribute to seeing uncertainty as an opportunity for growth and transcendence.

Keywords: hematopoietic stem cell transplantation, hematologic diseases, nursing, uncertainty

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Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: Moizza Tahir, Uzma Bashir, Aisha Akhtar, Zainab Ansari, Sameen Ansari, Muhammad Ali Tahir

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Cancer burden has globally increased. Among cutaneous cancers basal cell carcinoma constitute vast majority of skin cancer. There is need for appropriate diagnostic, therapeutic and prognostic significance evaluation for skin cancers Present study report intraoperative frozen section (FS) histopathological clearance for excision of BCC in a tertiary care center and find the frequency of involvement of surgical margin with reference to anatomical site, with size and surgical technique. It was prospective open label interventional study conducted at Dermatology department of tertiary care hospital Rawalpindi Pakistan in lais on with histopathology department from January 2023 to April 2024. Total of thirty-six (n = 36) patients between age 45-80 years with basal cell carcinoma of 10-20mm on face were included following inclusion exclusion criteria by purposive sampling technique. Informed consent was taken. Surgical excision was performed and intraoperative frozen section histopathology clearance of tumor margin was taken from histopathologist on telephone. Surgical reconstruction was done. Final Histopathology report was reexamined on day 10th for margin and depth clearance. Descriptive statistics were calculated for age, gender, sun exposure, reconstructive technique, anatomical site, and tumor free margin report on frozen section analysis. Chi square test was employed for statistical significance of involvement of surgical margin with reference to anatomical site, size and decision on reconstructive surgical technique, p value of <0.05 was considered significant. Total of 36 patients of BCC were enrolled, males 12 (33.3%) and females were 24 (66.6%). Age ranged from 45 year to 80 year mean of 58.36 ±SD7.8. Size of BCC ranged from 10mm to 35mm mean of 25mm ±SD 0.63. Morphology was nodular 18 (50%), superficial spreading 11(30.6%), morphoeic 1 (2.8%) and ulcerative in 6(16.7%) cases. Intraoperative frozen section for histopathological margin clearance with 2-3 mm safety margin and surgical technique has p-value0.51, for anatomical site p value 0.24 and size p-0.84. Intraoperative frozen section (FS) histopathological clearance for BCC face with 2-3mm safety margin with reference to reconstructive technique, anatomical site and size of BCC were insignificant.

Keywords: basal cell carcinoma, tumor free amrgin, basal cell carcinoma and frozen section, safety margin

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Authors: Taiwo O. Margaret, Olaoluwa O. Olaoluwa

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Moraceae family has immense phytochemical constituents and significant pharmacological properties, hence have great medicinal values. The aim of this study was to screen and quantify phytochemicals as well as the antioxidant activities of the leaf and stem bark extracts and fractions (crude ethanol extracts, n-hexane, ethyl acetate and aqueous ethanol fractions) of Ficus sagittifolia. Leaf and stem bark of F. sagittifolia were extracted by maceration method using ethanol to give ethanol crude extract. The ethanol crude extract was partitioned by n-hexane and ethyl-acetate to give their respective fractions. All the extracts were screened for their phytochemicals using standard methods. The total phenolic, flavonoid, tannin, saponin contents and antioxidant activity were determined by spectrophotometric method while the alkaloid content was evaluated by titrimetric method. The amount of total phenolic in extracts and fractions were estimated in comparison to gallic acid, whereas total flavonoids, tannins and saponins were estimated corresponding to quercetin, tannic acid and saponin respectively. 2, 2-diphenylpicryl hydrazyl radical (DPPH)* and phosphomolybdate methods were used to evaluate the antioxidant activities of leaf and stem bark of F. sagittifolia. Phytochemical screening revealed the presence of flavonoids, saponins, terpenoids/steroids, alkaloids for both extracts of leaf and stem bark of F. sagittifolia. The phenolic content of F. sagittifolia was most abundant in leaf ethanol crude extract as 3.53 ± 0.03 mg/g equivalent of gallic acid. Total flavonoids and tannins content were highest in stem bark aqueous ethanol fraction of F. sagittifolia estimated as 3.41 ± 0.08 mg/g equivalent of quercetin and 1.52 ± 0.05 mg/g equivalent of tannic acid respectively. The hexane leaf fraction of F. sagittifolia had the utmost saponin and alkaloid content as 5.10 ± 0.48 mg/g equivalent of saponins and 0.171 ± 0.39 g of alkaloids. Leaf aqueous ethanol fraction of F. sagittifolia showed high antioxidant activity (IC₅₀ value of 63.092 µg/mL) and stem ethanol crude extract (227.43 ± 0.78 mg/g equivalent of ascorbic acid) for DPPH and phosphomolybdate method respectively and the least active was found to be the stem hexane fraction using both methods (313.32 µg/mL; 16.21 ± 1.30 mg/g equivalent of ascorbic acid). The presence of these phytochemicals in the leaf and stem bark of F. sagittifolia are responsible for their therapeutic importance as well as the ability to scavenge free radicals in living systems.

Keywords: Moraceae, Ficus sagittifolia, phytochemicals, antioxidant

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Amin Masoumiganjgah, Luke Salmon, Julianne Burnton, Fahimeh Bagheri, Gavin Lenton, S. L. Ezekial Tan

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Introduction: The incidence of proximal biceps tenodesis and acute distal biceps repair is increasing, and rehabilitation protocols following both are variable. Golf is a popular sport within Australia, and the Gold Coast has become a Mecca for golfers, with more courses per capita than anywhere else in the world. Currently, there are no clear guidelines regarding return to golf play following biceps procedures. The aim of this study was to determine biceps brachii activation during the golf swing through electromyographic analysis, and subsequently, aid in rehabilitation guidelines and return to golf following tenodesis and repair. Methods: Subjects were amateur golfers with no previous upper limb surgery. Surface electromyography (EMG) and high-speed video recording were used to analyse activation of the left and right biceps brachii and the anterior deltoid during the golf swing. Each participant’s maximum voluntary contraction (MVC) was recorded, and they were then required to hit a golf ball aiming for specific distances of 2, 50, 100 and 150 metres at a driving range. Noraxon myoResearch and Matlab were used for data analysis. Mean % MVC was calculated for leading and trailing arms during the full swing and its’ 4 phases: back-swing, acceleration, early follow-through and late follow-through. Results: 12 golfers (2 female and 10 male), participated in the study. Median age was 27 (25 – 38), with all being right handed. Over all distances, the mean activation of the short and long head of biceps brachii was < 10% through the full swing. When breaking down the 50, 100 and 150m swing into phases, mean MVC activation was lowest in backswing (5.1%), followed by acceleration (9.7%), early follow-through (9.2%), and late follow-through (21.4%). There was more variation and slightly higher activation in the right biceps (trailing arm) in backswing, acceleration, and early follow-through; with higher activation in the leading arm in late follow-through (25.4% leading, 17.3% trailing). 2m putts resulted in low MVC values (3.1% ) with little variation across swing phases. There was considerable individual variation in results – one tense subject averaged 11.0% biceps MVC through the 2m putting stroke and others recorded peak mean MVC biceps activations of 68.9% at 50m, 101.3% at 100m, and 111.3% at 150m. Discussion: Previous studies have investigated the role of rotator cuff, spine, and hip muscles during the golf swing however, to our knowledge, this is the first study that investigates the activation of biceps brachii. Many rehabilitation programs following a biceps tenodesis or repair allow active range against gravity and restrict strengthening exercises until 6 weeks, and this does not appear to be associated with any adverse outcome. Previous studies demonstrate a range of < 10% MVC is similar to the unloaded biceps brachii during walking(1), active elbow flexion with the hand positioned either in pronation or supination will produce MVC < 20% throughout range(2) and elbow flexion with a 4kg dumbbell can produce mean MVC’s of around 40%(3). Our study demonstrates that increasing activation is associated with the leading arm, increasing shot distance and the late follow-through phase. Although the cohort mean MVC of the biceps brachii is <10% through the full swing, variability is high and biceps activation reach peak mean MVC’s of over 100% in different swing phases for some individuals. Given these EMG values, caution is advised when advising patients post biceps procedures to return to long distance golf shots, particularly when the leading arm is involved. Even though it would appear that putting would be as safe as having an unloaded hand out of a sling following biceps procedures, the variability of activation patterns across different golfers would lead us to caution against accelerated golf rehabilitation in those who may be particularly tense golfers. The 50m short iron shot was too long to consider as a chip shot and more work can be done in this area to determine the safety of chipping.

Keywords: electromyographic analysis, biceps brachii rupture, golf swing, tendon surgery

Procedia PDF Downloads 62

Authors: Bruno R. Mendes, Francisco J. Caldeira, Rita S. Luís

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Population ageing is directly correlated to an increase in medicine consumption. Beyond the latter and the polymedicated profile of elderly, it is possible to see a need for pharmacotherapeutic monitoring due to cognitive and physical impairment. In this sense, the tracking, organization and administration of medicines become a daily challenge and the pill-box dispenser system a solution. The pill-box dispenser (system) consists in a small compartmentalized container to unit dose organization, which means a container able to correlate the patient’s prescribed dose regimen and the time schedule of intake. In many European countries, this system is part of pharmacist’s role in clinical pharmacy. Despite this simple solution, therapy compliance is only possible if the patient adheres to the system, so it is important to establish a qualitative and quantitative analysis on the perception of the patient on the benefits and risks of the pill-box dispenser as well as the identification of the ideal system. The analysis was conducted through an observational study, based on the application of a standardized questionnaire structured with the numerical scale of Likert (5 levels) and previously validated on the population. The study was performed during a limited period of time and under a randomized sample of 188 participants. The questionnaire consisted of 22 questions: 6 background measures and 16 specific measures. The standards for the final comparative analysis were obtained through the state-of-the-art on the subject. The study carried out using the Likert scale afforded a degree of agreement and discordance between measures (Sample vs. Standard) of 56,25% and 43,75%, respectively. It was concluded that the pill-box dispenser has greater acceptance among a younger population, that was not the initial target of the system. However, this allows us to guarantee a high adherence in the future. Additionally, it was noted that the cost associated with this service is not a limiting factor for its use. The pill-box dispenser system, as currently implemented, demonstrates an important weakness regarding the quality and effectiveness of the medicines, which is not understood by the patient, revealing a significant lack of literacy when it concerns with medicine area. The characteristics of an ideal system remain unchanged, which means that the size, appearance and availability of information in the pill-box continue to be indispensable elements for the compliance with the system. The pill-box dispenser remains unsuitable regarding container size and the type of treatment to which it applies. Despite that, it might be a future standard for clinical pharmacy, allowing a differentiation of the pharmacist role, as well as a wider range of applications to other age groups and treatments.

Keywords: clinical pharmacy, medicines, patient safety, pill-box dispenser

Procedia PDF Downloads 178

Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

Procedia PDF Downloads 285

Authors: Emmanuel Ikechuckwu Onwubuya, Afees Adebayo Oladejo

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Background: The use of medicinal plants in the treatment of chronic diseases especially myocardial infarction, is gaining wide acceptance globally. Andrographis paniculata (Acanthaceae) is a medicinal plant commonly known as the king of bitters in Nigeria and has been acclaimed for several therapeutic activities. Materials and methods: This study investigated the cardio-protective effect of the leaf extract of A. paniculata in isoproterenol-induced myocardial infarction. Fresh green leaves of A paniculata were harvested from the Faculty of Agriculture farmland, Nnamdi Azikiwe University, Awka, Nigeria. Identification and authentication of the plant were carried out at the Department of Botany, Nnamdi Azikiwe University and a voucher specimen was deposited at the herbarium. The plant material was then shredded, air-dried under shade and pulverized. The fine powders obtained were weighed and extraction was done via a solvent combination of water and ethanol (3:7) for 72 hr via maceration. The filtrate gotten was evaporated to dryness to obtain the ethanol extract, which was used for further bioassay study. The bioactive constituents of the plant extract were quantitatively analyzed by Gas chromatography-mass spectrometry (GC-MS). The animals were administered the extract of A. paniculata orally for seven days at a divided dose of 100 mg/kg, 200 mg/kg and 400 mg/kg body weights. On the eighth day, myocardial infarction was induced through subcutaneous administration of isoproterenol at a dose of 150 mg/kg/day diluted in 2 ml of saline on two consecutive days. Subsequently, the blood pressures were monitored and blood was collected for bioassay studies. Results: The results of the study showed that the leaf extract of A. paniculata was rich in Dodecanoic acid (8.261%), 4-Dibenzofuranamine (6.03%), Cyclotrisiloxane (4.679 %). The findings also showed a significant decrease (p>0.05) in the Mean arterial blood pressure, heart rate, aspartate transaminase, alanine transaminase, creatinine kinase and lactate dehydrogenase activities of the treatment group compared with the untreated control group while the antioxidant (superoxide dismutase, catalase and glutathione) activities were significantly increased in the treatment group, compared with the untreated control group. Conclusion: The findings of this work have shown that the leaf of A. paniculata was rich in bioactive compounds, which could be synthesized to produce plant-based products to fight cardiovascular diseases, especially myocardial infarction.

Keywords: cardiovascular disease, myocardial infarction, medicinal plant, andrographis paniculata, isoproterenol

Procedia PDF Downloads 94

Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

Procedia PDF Downloads 507

Authors: Rajish Shil, Mohammad Ali Houri, Mohammad Milad Ismail, Fatimah Al Kaabi

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The clinical presentation of Primary hyperparathyroidism can vary from simple asymptomatic hypercalcemia to severe life-threatening hypercalcemic crisis with multi-organ dysfunction, which can be due to parathyroid adenoma or sometimes with malignant cancer. This cascade of clinical presentation can lead to a diagnostic and therapeutic challenge for treating the disease. We are presenting a case of severe hypercalcemic crisis due to parathyroid adenoma with an emphasis on early management, diagnosis, and interventions to prevent any lifelong complications and any permanent organ dysfunction. A 30 years old female with a history of primary Infertility, admitted to Al Ain Hospital critical care unit with Acute Severe Necrotizing Pancreatitis. She initially had a 1-month history of abdominal pain on and off, for which she was treated conservatively with no much improvement, and later on, she developed life-threatening severe pancreatitis, which required her to be admitted to the critical care unit. She was transferred from a private healthcare facility, where she was found to have a very high level of calcium up to 15mmol/L. She received systemic Zoledronic Acid, which lowered her calcium level transiently and later was increased again. She went on to develop multiple end-organ damages along with multiple electrolytes disturbances. She was found to have high levels of Parathyroid hormone, which was correlated with a parathyroid mass on the neck via radiological imaging. After a long course of medical treatment to lower the calcium to a near-normal level, parathyroidectomy was done, which showed parathyroid adenoma on histology. She developed hungry bone syndrome after the surgery and pancreatic pseudocyst after resolving of pancreatitis. She required aggressive treatment with Intravenous calcium for her hypocalcemia as she received zoledronic acid at the beginning of the disease. Later on, she was discharged on long term calcium and other electrolytes supplements. In patients presenting with hypercalcemia, it is prudent to investigate and start treatment early to prevent complications and end-organ damage from hypercalcemia and also to treat the primary cause of the hypercalcemia, with conscious follow up to prevent hypocalcemic complications after treatment. It is important to follow up patients with parathyroid adenomas for a long period in order to detect any recurrence of the tumor or to make sure if the primary tumor is either benign or malignant.

Keywords: hypercalcemia, pancreatitis, hypocalcemia, hyperparathyroidism

Procedia PDF Downloads 101

Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

Procedia PDF Downloads 245

Authors: Zenah Gheblawi, Susan Armijo-Olivo, Elisa B. Pelai, Vaishali Sharma, Musa Tashfeen, Angela Fung, Francisca Claveria

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Due to physiological differences between men and women, pain is experienced differently between the two sexes. Chronic pain disorders, notably temporomandibular disorders (TMDs), disproportionately affect women in diagnosis, and pain severity in opposition of their male counterparts. TMDs are a type of musculoskeletal disorder that target the masticatory muscles, temporalis muscle, and temporomandibular joints, causing considerable orofacial pain which can usually be referred to the neck and back. Therapeutic methods are scarce, and are not TMD-centered, with the latest research suggesting that subjects with chronic musculoskeletal pain disorders have abnormal alterations in the grey matter of their brains which can be remedied with exercise, and thus, decreasing the pain experienced. The aim of the study is to investigate the effects of exercise therapy in TMD female patients experiencing chronic jaw pain and to assess the consequential effects on brain activity. In a randomized controlled trial, the effectiveness of an exercise program to improve brain alterations and clinical outcomes in women with TMD pain will be tested. Women with chronic TMD pain will be randomized to either an intervention arm or a placebo control group. Women in the intervention arm will receive 8 weeks of progressive exercise of motor control training using visual feedback (MCTF) of the cervical muscles, twice per week. Women in the placebo arm will receive innocuous transcutaneous electrical nerve stimulation during 8 weeks as well. The primary outcomes will be changes in 1) pain, measured with the Visual Analogue Scale, 2) brain structure and networks, measured by fractional anisotropy (brain structure) and the blood-oxygen level dependent signal (brain networks). Outcomes will be measured at baseline, after 8 weeks of treatment, and 4 months after treatment ends and will determine effectiveness of MCTF in managing TMD, through improved clinical outcomes. Results will directly inform and guide clinicians in prescribing more effective interventions for women with TMD. This study is underway, and no results are available at this point. The results of this study will have substantial implications on the advancement in understanding the scope of plasticity the brain has in regards with pain, and how it can be used to improve the treatment and pain of women with TMD, and more generally, other musculoskeletal disorders.

Keywords: exercise therapy, musculoskeletal disorders, physical therapy, rehabilitation, tempomandibular disorders

Procedia PDF Downloads 274

Authors: A. Gramza-Michałowska, J. Skręty, M. Antczak, J. Kobus-Cisowska, D. Kmiecik, J. Korczak, Kulczyński Bartosz

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Background: Modern consumer highly appreciates the correlation between eating habits and health. Intensified research showed many proofs confirming that food besides its basic nutritional function, possess also significant prophylactic and therapeutic potential. Preventive potential of selected food is commonly used as improvement factor of patients life standard. World Health Organization indicates that diabetes (Diabetes mellitus) and obesity are two of the most common and dangerous diseases. Diet therapy is an element of diabetes education program and a part of healing process, allowing maintaining and remaining the optimal metabolic state of the system. It must be remembered that diabetes treatment should be individualized to each patient. One of highly recommended vegetable for diabetes is asparagus (Asparagus officinalis L.), low calories common plant, growing in European countries. Objective: To propose the technology of unsweetened muesli production with addition of new components, we investigated the effects of selected vegetable addition on antioxidative capacity and consumer’s acceptance of muesli as representative of breakfast product. Methods: Muesli was formulated from a composition of oat flakes, flaxseed, bran, carrots, broccoli and asparagus. Basic composition of muesli was evaluated as content of protein, lipids, fatty acid composition, ash, selected minerals and caloricity. Antioxidant capacity of muesli was evaluated with use radical scavenging methods (DPPH, ABTS), ORAC value and PCL - photochemiluminescence antiradical potential. Proposed muesli as new product was also characterized with sensory analysis, which included color, scent, taste, consistency and overall acceptance of a product. Results: Results showed that addition of freeze-dried asparagus into muesli allowed to lower the fat content and caloricity of a product according to the base product. No significant loss in antioxidant potential was evaluated, also the sensory value of a product was not negative. Conclusion: Designed muesli would be an answer for obese people looking for healthy snack during the daytime. Results showed that product with asparagus addition would be accepted by the consumers and because of its antidiabetic potential could be a n important factor in prevention of diabetes or obesity. Financial support by the UE Project no PO IG 01.01.00.00-061/09

Keywords: muesli, vegetables, asparagus, antioxidant potential, lipids

Procedia PDF Downloads 293

Authors: N. Khursheed, M. Fatima, S. Jamal, A. Raza, S. Rattani, Q. Ahsan, A. Rasheed, M. Jawed

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Introduction: Antibiotics are among the commonly prescribed medicines to treat bacterial infections. Their misuse intensifies resistance, and overuse incurs heavy losses to the healthcare system in terms of increased treatment costs and enhanced disease burden. Studies show that 40% of empirically used antibiotics are irrationally utilized. The objective of this study was to evaluate prescribing pattern of antibiotics at six public sector tertiary care hospitals across Pakistan. Methods: A multicenter cross-sectional point prevalence survey (PPS) was conducted in selected wards of six public sector tertiary care hospitals in Pakistan as part of the Clinical Engagement program by Fleming Fund Country Grant Pakistan in collaboration with Indus Hospital & Health Network (IHHN) from February to March 2021, these included Jinnah Postgraduate Medical Center and Dr. Ruth K. M. Pfau Civil Hospital from Karachi, Sheikh Zayed Hospital Lahore, Nishtar Medical University Hospital Multan, Medical Teaching Institute Hayatabad Medical Complex Peshawar, and Provincial Headquarters Hospital Gilgit. WHO PPS methodology was used for data collection (Hospital, ward, and patient level data was collected). Data was entered into the open-source Kobo Collect application and was analyzed using SPSS (version 22.0). Findings: Medical records of 837 in-patients were surveyed, of which the prevalence of antibiotics use was 78.5%. The most commonly prescribed antimicrobial was Ceftriaxone (21.7%) which is categorized in the Watch group of WHO AWaRe Classification, followed by Metronidazole (17.3%), Cefoperazone/Sulbactam (8.4%), Co-Amoxiclav (6.3%) and Piperacillin/Tazobactam (5.9%). The antibiotics were prescribed largely for surgical prophylaxis (36.7%), followed by community-acquired infections (24.7%). One antibiotic was prescribed to 46.7%, two to 39.9%, and three or more to 12.5 %. Two of six (30%) hospitals had functional drug and therapeutic committees, three (50%) had infection prevention and control committees, and one facility had an antibiotic formulary. Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasizes the importance of expanding the antimicrobial stewardship program. Mentoring clinical teams will help to rationalize antimicrobial use.

Keywords: antimicrobial resistance, antimicrobial stewardship, point prevalence survey, antibiotics

Procedia PDF Downloads 87

Authors: Donna Banks

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In 1998 Winston James called for more research on the Caribbean diaspora and this ethnographic study, incorporating participant observation, interviews, and archival research, adds to the scholarship in this area. The research is grounded in the discipline of cultural studies but is cross-disciplinary in nature, engaging anthropology, psychology, and urban planning. This paper centers on community murals and their contribution to a more culturally diverse and representative community. While many museums are in the process of reassessing their collection, acquiring works, and developing programming to be more inclusive, and public art programs are investing millions of dollars in trying to fashion an identity in which all residents can feel included, local artists in neighborhoods in many countries have been using community murals to tell their stories. Community murals serve a historical, political, and social purpose and are an instrumental strategy in creative placemaking projects. Community murals add to the livability of an area. Even though official measurements of livability do not include race, ethnicity, and gender - which are egregious omissions - murals are a way to integrate historically underrepresented people into the wider history of a country. This paper draws attention to a creative placemaking project in the port city of Bristol, England. A city, like many others, with a history of spacializing race and racializing space. For this reason, Bristol’s Seven Saints of St. Pauls® Art & Heritage Trail, which memorializes seven Caribbean-born social and political change agents, is examined. The Seven Saints of St. Pauls® Art & Heritage Trail is crucial to the city, as well as the country, in its contribution to the de-racialization of public spaces. Within British art history, with few exceptions, portraits of non-White people who are not depicted in a subordinate role have been absent. The artist of the mural project, Michelle Curtis, has changed this long-lasting racist and hegemonic narrative. By creating seven large-scale portraits of individuals not typically represented visually, the artist has added them into Britain’s story. In these murals, however, we see more than just the likeness of a person; we are presented with a visual commentary that reflects each Saint’s hybrid identity of being both Black Caribbean and British, as well as their social and political involvement. Additionally, because the mural project is part of a heritage trail, the murals' are therapeutic and contribute to improving the well-being of residents and strengthening their sense of belonging.

Keywords: belonging, murals, placemaking, representation

Procedia PDF Downloads 72

Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

Procedia PDF Downloads 54

Authors: Shao-Ying Wang, Shin-I Shih, Chi-Cheng Wu

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Background: By following to the maturity theory about age, the manifestation of depression in different age groups under occupational stressors still remains unclear. Therefore, the aim of this study was to examine the depression within four main symptoms clusters: cognition, affect, physical complaints and interpersonal difficulty among the different age groups. Additionally, this study also used the stress appraisal theory, through the examination of challenge and hindrance appraisals, the effects of cognitive factors were expected to give therapeutic indication for the future treatment of depression under abusive leadership. Methods (Participants and Procedure): The data were collected in two waves from employees of local companies in Taiwan. The participants (58 males and 167 females) were native Chinese speakers, ranging in age from 20 to 59 years (M= 36.51). Up to 80% educational level of participants were above senior high. The married population was approximately at 43%. Measures; 1. Abusive Leadership: To measure abusive leadership, we used 15-item scale of abusive supervision which anchored on a 7-point Likert-type scale. (α= .96) 2. Depression: We used Taiwanese Depression Scale to measure the 4 clusters (cognition, affect, physical complaints and interpersonal difficulty) of symptoms. Participants responded for depression anchored on a 7-point Likert-type scale (α= .96). 3. Stress Appraisal Scale: To measure challenge and hindrance types of appraisal, participants responded to 33-item measure anchored on a 7-point Likert-type scale. (Challenge appraisal; α= .90; hindrance appraisal α= .87). Results: The results of correlation showed that there was a significant and negative correlation between abusive leadership and age (r = - .21, p < .01). Abusive leadership was positive correlated significantly with hindrance appraisal (r = .52, p < .01) and depression (r = .20, p < .01). The results also showed that hindrance appraisal was correlated to depression positively (r = .36, p < .01). A one-way ANOVA was conducted to compare the effect of lower/middle/order age groups on each cluster of depressive symptoms. The results showed that the effect of age groups on cognition was significant F (2, 157) =3.66, P < .05. Older age group (M=13.43 SD=6.84) reported less cognitive symptoms of depression than the middle (M=16.77 SD=7.49) and lower age (M=16.91 SD=6.97) groups. Besides, the effect of age groups on affect was also significant F (2,157)= 4.09 P < .05. Older age group (M=18.68 SD=8.98) reported less affective symptoms of depression than the middle (M=22.01 SD=7.96) and lower age (M=23.56 SD=7.67) groups. Moreover, the main effect of hindrance appraisal was found F (2, 157) =3.81, P < .05. Older age group (M=9.44 SD=2.89) reported fewer score on hindrance appraisals than the middle (M=11.06 SD=4.02) and lower age (M=9.62 SD=3.17) groups. To conclude, the severity of depression symptoms varies across different age groups. Maturity seems to be the protective factor to depression, accompanying with lower hindrance appraisals.

Keywords: abusive leadership, affective commitment, depression symptoms, psychological well-being

Procedia PDF Downloads 186

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

Abstract:

The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 96

Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

Abstract:

Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

Procedia PDF Downloads 99

Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

Abstract:

Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

Procedia PDF Downloads 45