Search results for: pancreatic cyst

Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Muhammad Mazhar, Yong Zhu, Likang Qin

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Foods contain endogenous components known as dietary fibers, which are classified into soluble and insoluble forms. Dietary fibers are resistant to gut digestive enzymes, modulating anaerobic intestinal microbiota (AIM) and fabricating short-chain fatty acids (SCFAs). Acetate, butyrate, and propionate dominate in the gut, and different pathways, including Wood-Ljungdahl and acrylate pathways, generate these SCFAs. In pancreatic dysfunction, the release of insulin/glucagon is impaired, which leads to hyperglycemia. SCFAs enhance insulin sensitivity or secretion, beta-cell functions, leptin release, mitochondrial functions, and intestinal gluconeogenesis in human organs, which positively affect type 2 diabetes (T2D). Research models presented that SCFAs either enhance the release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L-cells (entero-endocrine) or promote the release of leptin hormone satiation in adipose tissues through G-protein receptors, i.e., GPR-41/GPR-43. Dietary fibers are the components of foods that influence AIM and produce SCFAs, which may be offering beneficial effects on T2D. This review addresses the effectiveness of SCFAs in modulating gut AIM in the fermentation of dietary fiber and their worth against T2D.

Keywords: dietary fibers, intestinal microbiota, short-chain fatty acids, fermentation, type 2 diabetes

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Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc

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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.

Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials

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Authors: Mahdieh Jajroudi

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Developing a pharmacokinetic model for the neuroendocrine tumors therapy agent 177Lu-DOTATATE in nude mice bearing AR42J rat pancreatic tumor to investigate and evaluate the behavior of the complex was the main purpose of this study. The utilization of compartmental analysis permits the mathematical differencing of tissues and organs to become acquainted with the concentration of activity in each fraction of interest. Biodistribution studies are onerous and troublesome to perform in humans, but such data can be obtained facilely in rodents. A physiologically based pharmacokinetic model for scaling up activity concentration in particular organs versus time was developed. The mathematical model exerts physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to forecast new complex distribution in humans' each organ. The concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 177Lu labeled somatostatin analogues was modeled and drawn as function of time. Conclusion: The variation of pharmaceutical concentration in all organs is characterized with summation of six to nine exponential terms and it approximates our experimental data with precision better than 1%.

Keywords: biodistribution modeling, compartmental analysis, 177Lu labeled somatostatin analogues, neuroendocrine tumors

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Authors: Mosaab A. Omara, Layla O. Elmajdoubb, Mohammad Saleh Al-Aboodyc, Ahmed ElSifyd, Ahmed O. Elkhtamd

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The aim of this study is to present the molecular characterization of cysticercus tenuicolis of Taenia hydatigena from livestock isolates in Egypt, using the amplification of sequencing of the mt-CO1 gene. We introduce a detailed image of the Cysticercus tenuicolis infection in ruminant animals in Upper Egypt. Cysticercus tenuicolis inhabits such organs in ruminants as the omentum, viscera, and liver. In the present study, the infection rate of Cysticercus tenuicolis was found to be 16% and 19% in sheep and goat sample respectively. Firstly we report one larval stage of Taenia hydatigena detected in the camel liver in Egypt. Cysticercus tenuicolis infection manifested a higher prevalence in females than in males. Those above 2 years of age manifested a higher infection rate than younger animals. The preferred site for the infection was the omentum: a 70% preference in sheep and a 68% preference in goat samples. The molecular characterization using the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene of isolates from sheep, goats and camels corresponded to T. hydatigena. For this study, molecular characterizations of T. hydatigena were done for the first time in Egypt. Molecular tools are of great assistance in characterizing the Cysticercus tenuicolis parasite especially when the morphological character cannot be detected because the metacestodes are frequently confused with infection by the Hydatid cyst, especially when these occur in the visceral organs. In the present study, Cysticercus tenuicolis manifested high identity in the goat and sheep samples, while differences were found more frequently in the camel samples (10 pairbase). Clearly molecular diagnosis for Cysticercus tenuicolis infection significantly helps to differentiate it from such other metacestodes.

Keywords: cysticercus tenuicolis, its2, genetic, qena, molecular and taenia hydatigena

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Authors: Venkat Garigapati

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Cell-based therapies are limited due to underlying host immune system activity. Microencapsulation of living cells to overcome this issue has some serious drawbacks, such as limitations of nutrient and oxygen diffusion, which pose a threat to the function and longevity of cells. The conformal coating could overcome the issues which are generally involved in traditional microencapsulation. Some of the theoretical advantages of conformal coating include superior nutrient and oxygen supply to cells, prolonged lifespan, improved drug-secreting cell functionality and an opportunity to load high cell doses in small volumes. Despite several advantages to the conformal coating, there are no suitable methods available to apply to living cells. The ultra-thin conformal coating was achieved utilizing click-reactive methacryloyloxyethyl phosphorylcholine (MPC) polymers, which are capable of specifically reacting one polymer to another at neutral pH in the aqueous isotonic system at the desired temperature suitable for living cells without the need of deleterious initiators. ARPE-19 (Adult Retinal Pigment Epithelial cell line-19) cell-spheroids and rat pancreatic islets were used in the formulation studies. The in vitro studies of coated ARPE-19 cell-spheroids and rat islets indicate that the coat was intact; cells were viable and functioning. The in vitro study results revealed that the conformal coating technology seems promising and in vivo studies are being planned.

Keywords: cells, hydrogel, conformal coating, microencapsulation, insulin

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Authors: Jaturong Matidtor, Krisna R. Torrissen, Saengtong Pongjareankit, Sudaporn Tongsiri, Jiraporn Rojtinnakorn

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Low survival rate has being particular problem in nursery of marble goby juvenile. The aim of this study was to investigate effect of garlic extract on protein digestive pancreatic enzymes, trypsin (T) and chymotrypsin (C). The marble goby were reared with commercial feed mixed garlic extract at concentration of 0 (control), 0.3, 0.5, 1.0, 3.0 and 5.0% (w/w) for 6 weeks. Analysis of the digestive enzymes at 2 and 6 weeks was performed. Growth parameters; weight gain (WG), specific growth rate (SGR) and feed efficiency (FE), were identified. For T, C and T/C at 2 weeks, values of T and T/C ratio of 0.3% (w/w) group showed significant difference (p < 0.05) with the highest values of 17685.64± 11981.77 U/mg protein and of 51.64 ± 27.46 U/mg protein, respectively. For C at 2 weeks, 0% (w/w) group showed the highest values of 16191.76± 2225.56 U/mg protein. Whereas value of T, C and T/C ratio at 6 weeks, there was no significant difference (p > 0.05). For growth performance, it significantly increased in all garlic extract fed groups (0.3-5.0%, w/w), both at 2 and 6 weeks. At 2 weeks, values of WG and SGR of 0.5% (w/w) group showed the highest values of 71.51 ± 1.60%, and 3.85 ± 0.07%, respectively. For FE, 0.3% (w/w) group showed the highest value of 60.21 ± 6.51%. At 6 weeks, it illustrated that all growth parameters of 5.0% (w/w) group were the highest values; WG = 35.06 ± 5.66%, SGR = 2.14 ± 0.30%, and FE = 5.86 ± 0.68%. We suggested that garlic extract could be available for protein digestive enzyme and growth enhancement in marble goby nursery with artificial feed. This result will be high benefit for commercial aquaculture of marble goby.

Keywords: marble goby, nursery, garlic extract, digestive enzyme, growth

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Authors: Ihab Saad Ahmed

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Background For Siewert type I and II gastroesophageal junction tumor (GEJ) laparoscopic proximal gastrectomy can be performed. It is associated with several perioperative benefits compared with open proximal gastrectomy. The use of laparoscopic proximal gastrectomy (LPG) has become an increasingly popular approach for select tumors Methods We describe our technique for LPG, including the preoperative work-up, illustrated images of the main principle steps of the surgery, and our postoperative course. Results Thirteen pts (nine males, four female) with type I, II (GEJ) adenocarcinoma had laparoscopic radical proximal gastrectomy and D2 lymphadenectomy. All of our patient received neoadjuvant chemotherapy, eleven patients had intrathoracic anastomosis through mini thoracotomy (two hand sewn end to end anastomoses and the other 9 patient end to side using circular stapler), two patients with intrathoracic anastomosis had flap and wrap technique, two patients had thoracoscopic esophageal and mediastinal lymph node dissection with cervical anastomosis The mean blood loss 80ml, no cases were converted to open. The mean operative time 250 minute Average LN retrieved 19-25, No sever complication such as leakage, stenosis, pancreatic fistula ,or intra-abdominal abscess were reported. Only One patient presented with empyema 1.5 month after discharge that was managed conservatively. Conclusion For carefully selected patients, LPG in GEJ tumour type I and II is a safe and reasonable alternative for open technique , which is associated with similar oncologic outcomes and low morbidity. It showed less blood loss, respiratory infections, with similar 1- and 3-year survival rates.

Keywords: LPG(laparoscopic proximal gastrectomy, GEJ( gastroesophageal junction tumour), d2 lymphadenectomy, neoadjuvant cth

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Authors: Susan Amirsalari, Azime Khosrinejad, Elham Rahimian

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Objective: Epilepsy is a common brain disorder characterized by a persistent tendency to develop in neurological, cognitive, and psychological contents. Magnetic Resonance Imaging (MRI) is a neuroimaging test facilitating the detection of structural epileptogenic lesions. This study aimed to compare the MRI findings between patients with intractable and drug-responsive epilepsy. Material & methods: This case-control study was conducted from 2007 to 2019. The research population encompassed all 1-16- year-old patients with intractable epilepsy referred to the Shafa Neuroscience Center (n=72) (a case group) and drug-responsive patients referred to the pediatric neurology clinic of Baqiyatallah Hospital (a control group). Results: There were 72 (23.5%) patients in the intractable epilepsy group and 200 (76.5%) patients in the drug-responsive group. The participants' mean age was 6.70 ±4.13 years, and there were 126 males and 106 females in this study Normal brain MRI was noticed in 21 (29.16%) patients in the case group and 184 (92.46%) patients in the control group. Neuronal migration disorder (NMD)was also exhibited in 7 (9.72%) patients in the case group and no patient in the control group. There were hippocampal abnormalities and focal lesions (mass, dysplasia, etc.) in 10 (13.88%) patients in the case group and only 1 (0.05%) patient in the control group. Gliosis and porencephalic cysts were presented in 3 (4.16%) patients in the case group and no patient in the control group. Cerebral and cerebellar atrophy was revealed in 8 (11.11%) patients in the case group and 4 (2.01%) patients in the control group. Corpus callosum agenesis, hydrocephalus, brain malacia, and developmental cyst were more frequent in the case group; however, the difference between the groups was not significant. Conclusion: The MRI findings such as hippocampal abnormalities, focal lesions (mass, dysplasia), NMD, porencephalic cysts, gliosis, and atrophy are significantly more frequent in children with intractable epilepsy than in those with drug-responsive epilepsy.

Keywords: magnetic resonance imaging, intractable epilepsy, drug responsive epilepsy, neuronal migrational disorder

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Authors: Sobhy El-Sohaimy, Abduvali Toshev, Hanem Mansour

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(1) Objective: The main objective of the current study was to evaluate in an In Vitro and In Vivo, the potential activity of olive leaves extract (OLE) in the treatment and/or preventing the diabetes mellitus type II and related implications; (2) Methodology: Five groups of male rats were used in the current study: group (1)- negative control (normal); group (2)- positive control, streptozotocin (STZ) induced rats; group (3)-diabetic rats treated with metformin (200 mg/kg) plus OLE (200 mg/kg); group 4- diabetic rats treated with metformin (200 mg/kg); group 5- diabetic rats treated with OLE (200 mg/kg). A four-week regime of oral treatment was administered once daily; (3) Results: Diabetic rats treated with metformin + OLE clearly showed normal blood glucose level (121.67 ± 5.49 mg/dl), and glycated hemoglobin (HbA1c) (3.70 ± 0.10%). The combination of metformin + OLE obviously showed a superior improvement in the lipid profile (TG, TC, HDL and LDL) compared to both metformin and OLE individually. The histological examination revealed that the combination of metformin + Olive leaves extract successfully repaired of the liver, kidneys, and pancreatic tissues in diabetic rats to be near to the normal status; (4) Conclusion: Finally, it can be concluded that, the combination of metformin and OLE exhibited a superior improvement than metformin and OLE individually which emphasized the promising adjuvant role of the OLE in the treatment protocol of diabetes mellitus type II.

Keywords: olive (olea europaea) leaves extracts, hypoglycemic agents, cytotoxicity, nitic oxide scavenging activity, α-glucose oxidase inhibitor

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Authors: Abinaya Balasubramanian, Satyabrata Ghosh, Satyahari Dey

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Non-Digestible Oligosaccharides(NDOs) are low molecular weight carbohydrates with degree of polymerization (DP) 3-20, that are delivered intact to the large intestine. NDOs are gaining attention as effective prebiotic molecules that facilitate prevention and treatment of several chronic diseases. Recently, NDOs are being obtained by cleaving complex polysaccharides as it results in high yield and also as the former tend to display greater bioactivity. Thelebolus sp. IITKGP BT-12, a recently identified psychrophilic, Ascomycetes fungus has been reported to produce a bioactive extracellular polysaccharide(EPS). The EPS has been proved to possess strong prebiotic activity and anti- proliferative effects. The current study is an attempt to identify and optimise the most suitable method for hydrolysis of the above mentioned novel EPS into NDOs, and further purify and characterise the same. Among physical, chemical and enzymatic methods, enzymatic hydrolysis was identified as the best method and the optimum hydrolysis conditions obtained using response surface methodology were: reaction time of 24h, β-(1,3) endo-glucanase concentration of 0.53U and substrate concentration of 10 mg/ml. The NDOs were purified using gel filtration chromatography and their molecular weights were determined using MALDI-TOF. The major fraction was found to have a DP of 7,8. The monomeric units of the NDOs were confirmed to be glucose using TLC and GCMS-MS analysis. The obtained oligosaccharides proved to be non-digestible when subjected to gastric acidity, salivary and pancreatic amylases and hence could serve as efficient prebiotics.

Keywords: characterisation, enzymatic hydrolysis, non-digestible oligosaccharides, response surface methodology

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Authors: Jiandong Ren, Lijun Zhao, Peng Chen

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Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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Authors: Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O Saleh, Manal Badawi

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Background: Diabetes is a metabolic disease that affects a wide range of people worldwide and results in serious complications. Streptozotocin (STZ) causes selective cytotoxicity in the pancreatic β-cell, and it has been extensively used to induce diabetes mellitus in rats. The present study investigated the effects of diosmin and chrysin alone or in combination with each other on glucose level and on liver in STZ diabetic rats. Methods: In this study, rats were divided into six experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with glycazide (10 mg/kg B.W, oral), treated STZ-diabetic with diosmin (100 mg/kg B. W., oral), treated STZ-diabetic with chrysin (80 mg/kg B.W., oral), treated STZ-diabetic with diosmin (50 mg/kg B.W, oral) + chrysin (40 mg/kg B.W., oral). After 2 weeks blood samples were withdrawn and glucose was measured. Animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for dissecting liver. Results: Throughout the experimental period, all treatments significantly (P<0.05) lowered serum glucose, AST, ALT, triglyceride, cholesterol, IL-6, TNF-α and IL-1β. Moreover, the treated diabetic rats showed higher levels of reduced glutathione (P<0.05) in the liver compared to the diabetic control rats and inhibited diabetes-induced elevation in the levels of malondialdehyde in liver. The results of this study clearly demonstrated that diosmin and chrysin possess several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects and anti-inflammatory effects. Conclusion: Considering these observations, it appears that diosmin and chrysin may be a useful supplement to delay the developmentof diabetes and its complications.

Keywords: diabetes, streptozocin, chrysin, rat, diosmin, cytokines

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Authors: Sajjad Jafari, Reza Akbari

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Background and Aim: Chrysin, a flavonoid compound found in medicinal plants, honey, and propolis, has potential biological activities that make it an important perspective in the treatment of infectious and cancer diseases. The aim of this review study is to evaluate the biological activities of chrysin in the treatment of infectious and cancer diseases. Material and Methods: The present study is a review study that searched reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using keywords such as antimicrobial, antifungal, chrysin, anticancer, antioxidants, and infectious diseases. The researchers examined 25 articles to determine the biological activities of chrysin. Results: Chrysin has high inhibitory or lethal activities on gram-positive and gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Enterococcus faeces. It also has anti-biofilm effects and antifungal effects on strains such as Aspergillus niger and Candida albicans. Chrysin also has anticancer effects on various cancers, including colorectal cancer, pancreatic cancer, breast cancer, and MCF-7 cancer, which have been confirmed in vitro and in vivo. Conclusion: Chrysin has the potential as an important therapeutic option in the treatment of infectious and cancer diseases. Its high antimicrobial and anticancer activities, combined with its low toxicity in nanoparticle form, make it a promising candidate for further clinical trials. The production of anti-microbial and anti-cancer drugs from natural substances, such as chrysin, is a valuable contribution to the field of medicine.

Keywords: chrysin, antimicrobial, anticancer, infectious diseases

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Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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Authors: Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Amornnat Thuppia, Nuntiya Somparn

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Several dietary and herbal plants have been shown to possess cytoprotective and antioxidant effects with various mechanisms of action. The aim of this study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Ocimum americanum (OA), commonly known as American basil or 'hoary basil', in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 100, 200 and 400 mg/kg for 28 days. Phytochemical screening of plant extracts revealed the presence of alkaloid, cardiac glycosides, tannin and steroid compounds. The extract contained phenolic compounds 36.91 ± 0.66 mg of gallic acid equivalents per gram OA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 41.27 ± 1.86 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. The protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased compared with normal control. Consistent with the induction of γ-GCL protein expression significantly reduction of serum oxidative stress marker malondialdehyde (MDA) was found in rat treated with OA extract compared with control. Taken together, this study provides evidence that Ocimum americanum exhibits direct antioxidant properties and can induce cytoprotective enzyme in vivo.

Keywords: antioxidant, γ-glutamylcysteine ligase, MDA, Ocimum americanum

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Gi-Young Park, Dong Rak Kwon, Sung Cheol Cho

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Objective: The synovium is known to be involved in many pathological characteristic processes. Also, synovitis is common in advanced osteoarthritis. We aimed to evaluate the clinical, radiographic, and ultrasound findings in patients with knee osteoarthritis and to compare the clinical and imaging findings between knee osteoarthritis with and without synovial hypertrophy confirmed by ultrasound. Methods: One hundred knees (54 left, 46 right) in 95 patients (64 women, 31 men; mean age, 65.9 years; range, 43-85 years) with knee osteoarthritis were recruited. The Visual Analogue Scale (VAS) was used to assess the intensity of knee pain. The severity of knee osteoarthritis was classified according to Kellgren and Lawrence's (K-L) grade on a radiograph. Ultrasound examination was performed by a physiatrist who had 24 years of experience in musculoskeletal ultrasound. Ultrasound findings, including the thickness of joint effusion in the suprapatellar pouch, synovial hypertrophy, infrapatellar tendinosis, meniscal tear or extrusion, and Baker cyst, were measured and detected. The thickness of knee joint effusion was measured at the maximal anterior-posterior diameter of fluid collection in the suprapatellar pouch. Synovial hypertrophy was identified as the soft tissue of variable echogenicity, which is poorly compressible and nondisplaceable by compression of an ultrasound transducer. The knees were divided into two groups according to the presence of synovial hypertrophy. The differences in clinical and imaging findings between the two groups were evaluated by independent t-test and chi-square test. Results: Synovial hypertrophy was detected in 48 knees of 100 knees on ultrasound. There were no significant differences in demographic parameters and VAS score except in sex between the two groups (P<0.05). Medial meniscal extrusion and tear were significantly more frequent in knees with synovial hypertrophy than those in knees without synovial hypertrophy. K-L grade and joint effusion thickness were greater in patients with synovial hypertrophy than those in patients without synovial hypertrophy (P<0.05). Conclusion: Synovial hypertrophy in knee osteoarthritis was associated with greater suprapatellar joint effusion and higher K-L grade and maybe a characteristic ultrasound feature of late knee osteoarthritis. These results suggest that synovial hypertrophy on ultrasound can be regarded as a predictor of rapid progression in patients with knee osteoarthritis.

Keywords: knee osteoarthritis, synovial hypertrophy, ultrasound, K-L grade

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Authors: Wai Prathumpai, Pranee Rachtawee, Sutamat Khajeeram, Pariya Na Nakorn

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The  β-glucan produced by Ophiocordyceps dipterigena BCC 2073 is a (1, 3)-β-D-glucan with highly branching O-6-linkedside chains that is resistant to acid hydrolysis (by hydrochloric acid and porcine pancreatic alpha-amylase). This β-glucan can be utilized as a prebiotic due to its advantageous structural and biological properties. The effects of using this β-glucan as the sole carbon source for the in vitro growth of two probiotic bacteria (L. acidophilus BCC 13938 and B. animalis ATCC 25527) were investigated. Compared with the effect of using 1% glucose or fructo-oligosaccharide (FOS) as the sole carbon source, using 1% β-glucan for this purpose showed that this prebiotic supported and stimulated the growth of both types of probiotic bacteria and induced them to produce the highest levels of metabolites during their growth. The highest levels of lactic and acetic acid, 10.04 g·L^-1 and 2.82 g·L^-1, respectively, were observed at 2 h of cultivation using glucose as the sole carbon source. Furthermore, the fermentation broth obtained using 1% β-glucan as the sole carbon source had greater antibacterial activity against selected pathogenic bacteria (B. subtilis TISTR 008, E. coli TISTR 780, and S. typhimurium TISTR 292) than did the broths prepared using glucose or FOS as the sole carbon source. The fermentation broth obtained by growing L. acidophilus BCC 13938 in the presence of β-glucan inhibited the growth of B. subtilis TISTR 008 by more than 70% and inhibited the growth of both S. typhimurium TISTR 292 and E. coli TISTR 780 by more than 90%. In conclusion, O. dipterigena BCC 2073 is a potential source of a β-glucan prebiotic that could be used for commercial production in the near future.

Keywords: beta-glucan, Ophiocordyceps dipterigena, prebiotic, probiotic, antimicrobial

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: Adrian Reynaldo Sudirman, Siti Farida, Aisyah Aminy Maulidina, Caren Andika Surbakti

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Sedentary lifestyle and imbalance consumption pattern has made metabolic syndrome as the global time bomb phenomenon in the world. The increasing tendency of people in consuming high amount of fructose and cholesterol food has worsened this issue in the society. Pancreas steatosis become one of the most comorbid when early diagnosis and prompt treatment has not been applied on hyperglycemic and hyperlipidemic condition in metabolic syndrome patient. Gemfibrozil become the drug of choice to prevent this issue, yet the efficacy of this regiment was still questionable. Acalypha indica Linn. is the herb that has protective effect on hyperlipidemic and hyperglycemic condition. This study was aimed to compare therapeutic effect of gemfibrozil (G) and Acalypha indica Linn. (AI) on high fructose and cholesterol diet-induced pancreas steatosis in Sprague-Dawley mice. The post induction mice were divided into four groups: control, gemfibrozil, AI extract, and G+AI combination regiment. Each group received four weeks intervention. The result of statistical analysis using the One-Way ANOVA test and Tukey Post Hoc test showed significant decrease in pancreatic steatosis between the control group and administered Acalypha indica group (p = 0.004, 95% CI: 0.170-0.959) and the group administered with a combination of Gemfibrozil-Acalypha indica (p = 0.023, 95% CI: 0.537-0.813). The protective effect of Acalypha indica Linn. shows that this plant has the potential as therapeutic option in overcoming the condition of pancreas steatosis in metabolic syndrome.

Keywords: Acalypha Indica Linn., Cholesterol, Fructose, Gemfibrozil, Pancreas Steatosis

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Authors: Thaer Khaleel Swaid, Maryam Al Ahmad, Ishtiaq Ahmad

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47-year-old female, known to have a liver cyst and hemangiomas, presented to the gastroenterology clinic for chronic moderate postprandial epigastric pain, which is aggravated by food, leaning forward and relieved on lying flat. The pain was associated with nausea, vomiting, heartburn and excessive burping. She opened her bowel daily, having well-formed stools without blood or mucus. The patient denied NSAID intake, smoking or alcohol. On physical examination during the episode of pain abdomen revealed a soft, lax abdomen and mild tenderness in the epigastric region without organomegaly. Bowel sounds were audible. Her routine hematological and biochemical parameters were within normal, including CBC, Celiac serology, Lipase, Metabolic profile and H pylori stool antigen. The patient underwent an Ultrasound of the abdomen which showed multiple liver cysts, hemangioma, normal GB and biliary tree. Based on the clinical picture and to narrow our differential diagnosis, an ultrasound Doppler for the abdomen was ordered, and it showed celiac artery peak systolic velocity in expiration is 270cm/s, suggestive of median arcuate ligament syndrome. She Had computerized tomography abdomen done and showed a Narrowing of the celiac artery at the origin, likely secondary to low insertion of the median arcuate ligament. Furthermore, Gastroscopy and, later on colonoscopy were done, which was unremarkable. A laparoscopic decompression of the celiac trunk was indicated, for which the patient was referred to vascular surgery. This case confirms that Median Arcuate Ligament syndrome is an unusual diagnosis and is always challenging. Usually, patients undergo extensive workups before a final diagnosis is achieved. Our case highlights the challenge of diagnosing MALS since this entity is rare. It is a good choice to perform abdominal ultrasound with Doppler imaging on a patient with symptoms such as postprandial angina.

Keywords: Unveiling the Mystery, MALS, rare entity, Rare vascular phenomenon

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Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

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Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

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Authors: Alexandru Grigorescu, Alexandra Protesanu

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Background: Approximately 34-67 percent of cancer patients experience an episode of uncontrolled pain during the course of their disease, depending on the stage. The aim is to provide evidence-based data for pain prevalence, diagnosis and treatment recommendations on an integrative model of medical oncology and palliative care for patients with cancer diagnostic in a day hospital. Patients and method: Consultation registers and electronic records of 166 Patients (Pts) were studied from April 2022 to March 2023. Pts with pain syndrome were selected. The pain was objectified by the visual pain scale. To elucidate the causes of the pain, investigations were carried out: bone scintigraphy, CT scan, and PET-CT. The analgesic treatments were represented by weak and strong morphine, radiotherapy, and bisphosphonates. Result: During the mentioned period, 166 oncological patients (74 women and 92 men) were treated in the oncology day hospitalization service. There were 1,500 consultations, 40 of which were only for pain. The neoplastic locations were: gynecological, malignant melanoma, breast, gastric, bronchopulmonary, colorectal, liver, pancreatic, bladder, and kidney. 70 Pts presented pain syndrome. The causes of the pain were represented by bone metastases, compressive tumors, and post-surgical status. Drug treatment: Tramadol 47 Pts, of which 10 switched to a major opioid (Oxycodonum, Morphine sulfate), 20 Pts were treated with Oxycodonum as the first intention. In 5 patients ry to rotated morphine, 20 Pts received palliative radiotherapy, 10 Pts were treated with bisphosphonates. 2 Pts required neurosurgery consultation for an antalgic intervention. 5 Pts had important adverse reactions to morphine. All patients and their families were advised by a medical oncologist and psychologist for a lifestyle change. Conclusions: The prevalence of pain was similar to that described in the literature. In most cases, the pain could be managed in the day hospital. Weak and strong morphine represented the main pain therapy. Palliative radiotherapy was the second most effective therapy. Treatment with bisphosphonates was useful. Surgical interventions were rarely indicated. Discussions with patients and their families regarding the lifestyle change were important.

Keywords: cancer pain, opioids, medical oncology, palliative care

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin

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Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.

Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol

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