Search results for: anti cancerous

Authors: Siva Chander Chabattula, Piyush Kumar Gupta, Debashis Chakraborty, Rama Shanker Verma

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Green nanoparticles have gotten a lot of attention because of their potential applications in tissue regeneration, bioimaging, wound healing, and cancer therapy. The physical and chemical methods to synthesize metal oxide nanoparticles have an environmental impact, necessitating the development of an environmentally friendly green strategy for nanoparticle synthesis. In this study, we used Annona muricata plant leaf extract to synthesize Zinc Oxide nanoparticles (Am-ZnO NPs), which were evaluated using UV/Visible spectroscopy, FTIR spectroscopy, X-Ray Diffraction, DLS, and Zeta potential. Nanoparticles had an optical absorbance of 355 nm and a net negative surface charge of ~ - 2.59 mV. Transmission Electron Microscope characterizes the Shape and size of the nanoparticles. The obtained Am-ZnO NPs are biocompatible and hemocompatible in nature. These nanoparticles caused an anti-cancer therapeutic effect in MIA PaCa2 and MOLT4 cancer cells by inducing oxidative stress, and a change in mitochondrial membrane potential leads to programmed cell death. Further, we observed a reduction in the size of lung cancer spheroids (act as tumor micro-environment) with doxorubicin as a positive control.

Keywords: Biomaterials, nanoparticle, anticancer activity, ZnO nanoparticles

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Authors: Leslie M. Mullins

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In the face of dramatically shifting demographic trends and macroeconomic pressures on affordable housing in high-cost cities, municipalities and developers have been forced to develop new models of sustainable development that integrates elements of substantial rehabilitation and new construction while controlling for relocation and mass displacement. Community development partners in the San Francisco Bay Area of Northern California are starting to prioritize anti-displacement strategies when rehabilitating severely neglected public housing developments. This study explored the community-driven efforts to transform four dilapidated public housing sites (N=2,600 households) into thriving mixed-income housing communities. Eight interviews were conducted with frontline workers (property managers and service providers), who directly worked with residents throughout critical stages of the relocation and leasing process. Interviews were audio-recorded, transcribed, and analyzed by a systematic procedure for qualitative analysis to identify key themes on the topics of interest. Also, an extensive literature analysis was conducted to determine promising practices throughout the industry. This study highlighted that resident’s emotional attachment to their homes (regardless of the deteriorating conditions of their unit) could both a) impede the relocation process and substantially impact the budget and timeline, while b) simultaneously providing a basis for an enhanced sense of belonging and community cohesion. This phenomenon often includes the welcoming of new residents and cultures. Resident centered workshops, healing centered rituals, and extensive 'hands-on' guidance was highlighted as promising practices that resulted in residential retention rates that were two to three times the national average and positively impacted the overall project’s budget and timeline.

Keywords: anti-displacement strategies, community based practices, community cohesion, cultural preservation, healing-centered, public housing, relocation, trauma-informed

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Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: V. S. S. Kumar, V. Ramya

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In the modern electronic warfare, the signal scenario is changing at a rapid pace with the introduction of Low Probability of Intercept (LPI) radars. In the modern battlefield, radar system faces serious threats from passive intercept receivers such as Electronic Attack (EA) and Anti-Radiation Missiles (ARMs). To perform necessary target detection and tracking and simultaneously hide themselves from enemy attack, radar systems should be LPI. These LPI radars use a variety of complex signal modulation schemes together with pulse compression with the aid of advancement in signal processing capabilities of the radar such that the radar performs target detection and tracking while simultaneously hiding enemy from attack such as EA etc., thus posing a major challenge to the ES/ELINT receivers. Today an increasing number of LPI radars are being introduced into the modern platforms and weapon systems so these LPI radars created a requirement for the armed forces to develop new techniques, strategies and equipment to counter them. This paper presents various modulation techniques used in generation of LPI signals and development of Time Frequency Algorithms to analyse those signals.

Keywords: anti-radiation missiles, cross terms, electronic attack, electronic intelligence, electronic warfare, intercept receiver, low probability of intercept

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Authors: Sangeeta Girdhar, Amanat Grewal, Nahush Bansal

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Introduction: There is an increasing burden of hypertension in India. The morbidity and mortality arising from complications are mainly due to non-adherence to medication, unhealthy dietary habits, and lack of physical activity. Non-adherence is a well-recognised factor contributing to inadequate control of high blood pressure. Adherence to pharmacotherapy for hypertension varies from 43% to 88%. Non-adherence is influenced by various socio-demographic factors. Understanding these factors is useful in managing non-adherence. Therefore, the study was planned to determine adherence among hypertensives and factors associated with non-adherence to treatment. Methodology: A cross-sectional study was conducted at Urban Health Training Centre of Dayanand Medical College and Hospital Ludhiana. Patients attending the OPD over a period of 3 months were included in the study. Prior ethical approval was obtained, and informed consent was taken from subjects. A predesigned semi-structured questionnaire was applied, which included socio-demographic profile, treatment-seeking behaviour, adherence to the antihypertensive medication, lifestyle factors (intake of alcohol, smoking, consumption of junk food, high salt intake) contributing to the development of the disease. Reasons for non-adherence to the therapy were also explored. Data was entered into excel, and SPSS 26 version was used for analysis. Results: A total of 186 individuals were interviewed. Out of these, 113 females (60.8%) and 73 males (39.2%) participated in the study. Mean age of participants was 60.9 ± 10.7 years. Adherence to anti-hypertensive treatment was found in 68.3% of the participants. It was observed that adherence was more in literate individuals as compared to illiterate (p value- 0.78). Adherence was lower among smokers (33.3%) and alcohol consumers (53.8%) as compared to non-users (69.4% and 70.6%, respectively). The predominant reasons for skipping medications were discontinuing medication when feeling well, forgetfulness and unawareness. Conclusion: There is a need to generate awareness regarding the importance of adherence to therapy among patients. Intensive health education and counselling of the patients is the need of the hour.

Keywords: hypertension, anti-hypertensive, adherence, counselling

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Authors: Yukinori Taniguchi, Kazuyoshi Kurita, Kohei Mizuta, Keigo Nishitani, Ryuichi Fukuda

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Tungsten carbide is widely used as a tool material in metal manufacturing process. Since tungsten is typical rare metal, establishment of recycle process of tungsten carbide tools and restore into cemented carbide material bring great impact to metal manufacturing industry. Recently, recycle process of tungsten carbide has been developed and established gradually. However, the demands for quality of cemented carbide tool are quite severe because hardness, toughness, anti-wear ability, heat resistance, fatigue strength and so on should be guaranteed for precision machining and tool life. Currently, it is hard to restore the recycled tungsten carbide powder entirely as raw material for new processed cemented carbide tool. In this study, to suggest positive use of recycled tungsten carbide powder, we have tried to fabricate a carbon based sintered steel which shows reinforced mechanical properties with recycled tungsten carbide powder. We have made set of newly designed sintered steels. Compression test of sintered specimen in density ratio of 0.85 (which means 15% porosity inside) has been conducted. As results, at least 1.7 times higher in nominal strength in the amount of 7.0 wt.% was shown in recycled WC powder. The strength reached to over 600 MPa for the Fe-WC-Co-Cu sintered alloy. Wear test has been conducted by using ball-on-disk type friction tester using 5 mm diameter ball with normal force of 2 N in the dry conditions. Wear amount after 1,000 m running distance shows that about 1.5 times longer life was shown in designed sintered alloy. Since results of tensile test showed that same tendency in previous testing, it is concluded that designed sintered alloy can be used for several mechanical parts with special strength and anti-wear ability in relatively low cost due to recycled tungsten carbide powder.

Keywords: tungsten carbide, recycle process, compression test, powder metallurgy, anti-wear ability

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Authors: Rahul Agarwal, Ashutosh Singh

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Cervical cancer is one of the women related cancers which starts from the pre-cancerous cells and a fraction of women with pre-cancers of the cervix will develop cervical cancer. Cervical pre-cancers if treated in pre-invasive stage can prevent almost all true cervical squamous cell carcinoma. The present study investigates the genes and pathways that are involved in the progression of cervical cancer and are responsible in transition from pre-invasive stage to other advanced invasive stages. The study used GDS3292 microarray data to identify the stage specific genes in cervical cancer and further to generate the network of the significant genes. The microarray data GDS3292 consists of the expression profiling of 10 normal cervices, 7 HSILs and 21 SCCs samples. The study identifies 70 upregulated and 37 downregulated genes in HSIL stage while 95 upregulated and 60 downregulated genes in SCC stages. Biological process including cell communication, signal transduction are highly enriched in both HSIL and SCC stages of cervical cancer. Further, the ppi interaction of genes involved in HSIL and SCC stages helps in identifying the interacting partners. This work may lead to the identification of potential diagnostic biomarker which can be utilized for early stage detection.

Keywords: cervical cancer, HSIL, microarray, SCC

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Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra

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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.

Keywords: Bid, Bcl-xl, UVC, apoptosis

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Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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Authors: Joseph L. Mathew, Shourjendra N. Banerjee, R. K. Ratho, Sourabh Dutta, Vanita Suri

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Background: In India and many other developing countries, a single dose of measles vaccine is administered to infants at 9 months of age. This is based on the assumption that maternal transplacentally transferred antibodies will protect infants until that age. However, our previous data showed that most infants lose maternal anti-measles antibodies before 6 months of age, making them susceptible to measles before vaccination at 9 months. Objective: This prospective study was designed to compare susceptibility in pre-term vs term infants, at different time points. Material and Methods: Following Institutional Ethics Committee approval and a formal informed consent process, venous blood was drawn from a cohort of 45 consecutive term infants and 45 consecutive pre-term infants (both groups delivered by the vaginal route); at birth, 3 months, 6 months and 9 months (prior to measles vaccination). Serum was separated and anti-measles IgG antibody levels were measured by quantitative ELISA kits (with sensitivity and specificity > 95%). Susceptibility to measles was defined as antibody titre < 200mIU/ml. The mean antibody levels were compared between the two groups at the four time points. Results: The mean gestation of term babies was 38.5±1.2 weeks; and pre-term babies 34.7±2.8 weeks. The respective mean birth weights were 2655±215g and 1985±175g. Reliable maternal vaccination record was available in only 7 of the 90 mothers. Mean anti-measles IgG antibody (±SD) in terms babies was 3165±533 IU/ml at birth, 1074±272 IU/ml at 3 months, 314±153 IU/ml at 6 months, and 68±21 IU/ml at 9 months. The corresponding levels in pre-term babies were 2875±612 IU/ml, 948±377 IU/ml, 265±98 IU/ml, and 72±33 IU/ml at 9 months (p > 0.05 for all inter-group comparisons). The proportion of susceptible term infants at birth, 3months, 6months and 9months was 0%, 16%, 67% and 96%. The corresponding proportions in the pre-term infants were 0%, 29%, 82%, and 100% (p > 0.05 for all inter-group comparisons). Conclusion: Majority of infants are susceptible to measles before 9 months of age suggesting the need to anticipate measles vaccination, but there was no statistically significant difference between the proportion of susceptible term and pre-term infants, at any of the four-time points. A larger study is required to confirm these findings and compare sero-protection if vaccination is anticipated to be administered between 6 and 9 months.

Keywords: measles, preterm, susceptibility, term infant

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Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

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Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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Authors: Abdolreza Esmaeilzadeh, Maryam Erfanmanesh, Sousan Ghasemi, Farzaneh Mohammadi

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Background: Hepatitis C Virus (HCV), a public health problem, is an enveloped, single-stranded RNA virus and a member of the Hepacivirus genus of the Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the outcomes of chronic infection with HCV. HCV isolates show significant heterogeneity in genetics around the world. Therefore, determining HCV genotypes is a vital step in determining prognosis and planning therapeutic strategies. Materials and Methods: Serum samples of 136 patients were collected and analyzed for anti-HCV antibodies using ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were exposed to RT-PCR, which was performed under standard condition. Afterwards, they investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype 2.0 line probe assay (LiPA). Results: Samples indicated 216 bp bands on 2% agarose gel. Analyses of the results demonstrated that the most dominant subtype was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b, 1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively. The frequency of unknown HCV genotypes was 4.41%. Conclusions: According to the results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a. Analysis of the results provides identification of certain HCV genotypes, and these valuable findings could affect the type and duration of the treatment.

Keywords: anti-HCV antibody, Hepatitis C Virus (HCV), genotype, RT-PCR, AS-PCR

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: Annunziata Albano

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Intimate Partner Violence (IPV) and Non-Partner Sexual Violence (NPSV) are still the most common forms of interpersonal violence against women today, and numerous studies have shown how they can affect women's physical and psychological well-being, frequently leading to depression, posttraumatic stress disorder (PTSD), and substance abuse. The primary goal of Italian Anti-Violence Centres (AVCs) is to provide an appropriate context for women to embark on a personalised path out of violence by providing various services such as listening groups, psychological and legal support, housing support in collaboration with shelters, work orientation, and specific support in the case of minor children. However, their physical environment is frequently overlooked, partly because these centres are typically established in pre-existing buildings and have a limited budget. Several studies on healthcare design and mental health, on the other hand, emphasise the potential of the built environment to facilitate healing by providing a restorative setting that aids in coping with stress and traumatic experiences, investigating the positive role of natural features and sensorial qualities such as light, colours, sound, and smell. This research aims to collect and summarise the key evidence-based principles derived from a multidisciplinary literature review about interior design elements that can help women recover after their traumatic experience. Furthermore, the study examines multiple case studies of Italian AVCs through the lens of previously determined principles, to understand how and whether these guidelines have been applied and which outcomes can provide relevant insights for design practice, with an emphasis on sensory qualities, usually overlooked in favour of other requirements. The outlined guidelines may serve as a framework for various typologies of services provided to women who are the victims of interpersonal violence, such as women's crisis centres and shelters.

Keywords: anti-violence centres, environmental psychology, interior design, interpersonal violence, restorative environments

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Authors: Eman Abdullah Morsi, Hend Okasha, Heba Abdel Hady, Mortada El-Sayed, Mohamed Abbas Shemis

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Context: Linum usitatissimum (Linn), known as Flaxseed, is one of the most important medicinal plants traditionally used for various health as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents as well as evaluate the antioxidant using α, α-diphenyl-β-picrylhydrazyl (DPPH), 2-2'azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and total antioxidant capacity (TAC) assay and investigation of anti-inflammatory by Bovine serum albumin (BSA) and anticancer activities of hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7) have been applied on hexane, ethyl acetate, n-butanol and methanol extracts and also, fractions of methonal extract (hexane, ethyl acetate and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts and fractions of methanolic extract were tested on (HepG2) and (MCF7). Results: Methanolic extract and its ethyl acetate fraction contain higher contents of total phenols and flavonoids. In addition, methanolic extract had higher antioxidant activity. Butanolic and ethyl acetate fractions yielded higher percent of inhibition of protein denaturation. Meanwhile, ethyl acetate fraction and methanolic extract had anticancer activity against HepG2 and MCF7 (IC50=60 ± 0.24 and 29.4 ± 0.12µg.mL⁻¹) and (IC50=94.7 ± 0.21 and 227 ± 0.48µg.mL⁻¹), respectively. In Gas chromatography-mass spectrometry (GC-MS) analysis, methanolic extract has 32 compounds, whereas; ethyl acetate and butanol fractions contain 40 and 36 compounds, respectively. Conclusion: Flaxseed contains totally different biologically active compounds that have been found to possess good variable activities, which can protect human body against several diseases.

Keywords: phenolic content, flavonoid content, HepG2, MCF7, hemolysis-assay, flaxseed

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Authors: Latife Merve Oktay, Berrin Tugrul

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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

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Authors: Michael Augustus Akagbor

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Same-sex relationships have always existed in Ghana. In coastal towns such as James Town in the heart of the country’s capital, persons who were sexually different and attracted to members of their own sex were able to live their lives openly as queer persons without any fear for their lives. Since 2006, this idyllic existence has been under attack, with LGBTQ+ communities suffering violence and discrimination. This paper highlights the lived experiences of the LGBTIQ+ community in Ghana against the backdrop of the anti-gay bill - The Promotion of Proper Human Sexual Rights and Ghanaian Family Values Bill, 2021 (now renamed the Human Sexual Rights and Family Values Bill, 2021), currently before Parliament, introduced by eight members of Parliament as a Private Members’ Bill, and its implications for the LGBTQ+ community. The paper makes recommendations to key stakeholders on strategies to counter the cultural and religious arguments/strategies and activism of the anti-LGBTQ+ movement in Ghana. It relied on secondary data from a variety of sources, including the Bill before Parliament, media reports, and baseline surveys and studies conducted by LGBTQ organizations and other Civil Society Organizations (CSOs) in Ghana and elsewhere.

Keywords: sexual rights, promotion, family values, lgbtq+, ghana, discrimination

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Authors: Najla M. Salkho, Vinod Paul, Pierre Kawak, Rute F. Vitor, Ana M. Martin, Nahid Awad, Mohammad Al Sayah, Ghaleb A. Husseini

Abstract:

Liposomes are popular lipid bilayer nanoparticles that are highly efficient in encapsulating both hydrophilic and hydrophobic therapeutic drugs. Liposomes promote a low risk controlled release of the drug avoiding the side effects of the conventional chemotherapy. One of the great potentials of liposomes is the ability to attach a wide range of ligands to their surface producing ligand-mediated active targeting of cancer tumour with limited adverse off-target effects. Ultrasound can also aid in the controlled and specified release of the drug from the liposomes by breaking it apart and releasing the drug in the specific location where the ultrasound is applied. Our research focuses on the synthesis of PEGylated liposomes (contain poly-ethylene glycol) encapsulated with the model drug calcein and studying the effect of low frequency ultrasound applied at different power densities on calcein release. In addition, moieties are attached to the surface of the liposomes for specific targeting of the cancerous cells which over-express the receptors of these moieties, ultrasound is then applied and the release results are compared with the moiety free liposomes. The results showed that attaching these moieties to the surface of the PEGylated liposomes not only enhance their active targeting but also stimulate calcein release from these liposomes.

Keywords: active targeting, liposomes, moieties, ultrasound

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Authors: Christen Kutz

Abstract:

Objective: The aim of this study is to review a case series of 4 high-level Olympic and Division 1 wrestlers who experienced debilitating posterior circulation ischemic strokes during or after a competitive wrestling event and to identify risk factors, etiology and outcomes of stroke in young, healthy elite wrestlers. Background: Stroke occurs in one in 10,000 people under age 64. In young adults, the most common causes of stroke are cardiac embolism, hypercoagulable state, and vasculopathy. One-third of these strokes occur in young, fit individuals. There is little published literature about ischemic strokes that occur in wrestlers. Based on the nature of wrestling, the risk of injury or dissection to neurovascular structures may be a possible theory, but very few case reports exist. Methodology: 4 wrestlers under the age of 44 with a known history of ischemic stroke participated in individual interviews either in person or virtually. Each of the wrestlers provided their demographic information, wrestling background, clinical presentation at the time of stroke, imaging results, identification of potential risk factors, acute treatment and recovery. Results: 3 white male Division 1 wrestlers (2 Lehigh University, 1 Lock Haven University) and 1 black male 2008 Olympian experienced posterior circulation strokes. Case #1 felt a “pop” while wrestling (lateral medullary infarct, possible vertebral artery dissection); Case #2 awoke with severe vertigo, sweating, and vomiting after wrestling the previous day (left cerebellar infarct, (+) protein S deficiency); Case #3 severe vertigo, ataxia, and sensation of impending doom after wrestling earlier that week (left cerebellar infarct, hypoplastic left vertebral artery (+) anti-cardiolipin antibodies). Case #4 severe dizziness, confusion (left cerebellar stroke, vertebral artery dissection, small PFO). Conclusion: 3 wrestlers were started on anti-platelet therapy, risk factors were modified, and returned to their sport. 1 wrestler was placed on anti-coagulation and retired from competition.

Keywords: stroke, wrestling, Olympic, posterior circulation

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Authors: Salwa A. H. Hamdi, Maha A. M. El-Shazly, Mona Fathi Fol, Hanan S. Mossalem, Mosad A. Ghareeb, Amina M. Ibrahim

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One of the most distinctive and defining features of cephalopods squid, cuttlefish, and Octopus is their inking behavior. Their ink, which is blackened by melanin but also contains other constituents, has been used by humans in various ways for millennia. The present study aims to investigate the chemical profiling of the Octopus vulgaris ink extract and to evaluate its antioxidant, antimicrobial, and anti-schistosomal activities. The present results showed that GC-MS examination of Octopus vulgaris ink comprises 21 compounds. The main detected compounds are (E)-1, 2, 3, 4-Tetra (4-phenylphenyl)-2-butene-1,4-dione, Lipo-3-episapelin A, and 5,10-Dihexyltetrabenzoporphyrin. Results showed that the octopus ink had antioxidant capacity and the capability to mask DPPH free radicals in comparison with ascorbic acid. Octopus Vulgaris ink extract had inhibitory action against three gram-positive bacteria, Streptococcus faecalis, Staphylococcus aureus, and Bacillus subtilis, and three gram-negative bacteria, Neisseria gonorrhoeae, Escherichia coli, and Pseudomonas aeuroginosa. Additionally, the extracted ink revealed antifungal activity against Aspergillus flavus and yeast as Candida albicans. The obtained data indicated the effectiveness of ink extract in pharmaceutical industries as an antioxidant, antimicrobial and antischistosomicidal

Keywords: antimicrobial, antioxidant, ink, octopus vulgaris

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Authors: Shoubhik Mandal, Debarghya Mallick, Abhishek Banerjee, R. Ganesan, P. S. Anil Kumar

Abstract:

We report magnetotransport measurements in Bi₁Sb₁Te₁.₅Se₁.₅/RuCl₃ heterostructure nanodevices. Bi₁Sb₁Te₁.₅Se₁.₅ (BSTS) is a strong three-dimensional topological insulator (3D-TI) that hosts conducting topological surface states (TSS) enclosing an insulating bulk. α-RuCl₃ (namely, RuCl₃) is an anti-ferromagnet that is predicted to behave as a Kitaev-like quantum spin liquid carrying Majorana excitations. Temperature (T)-dependent resistivity measurements show the interplay between parallel bulk and surface transport channels. At T < 150 K, surface state transport dominates over bulk transport. Multi-channel weak anti-localization (WAL) is observed, as a sharp cusp in the magnetoconductivity, indicating strong spin-orbit coupling. The presence of top and bottom topological surface states (TSS), including a pair of electrically coupled Rashba surface states (RSS), are indicated. Non-linear Hall effect, explained by a two-band model, further supports this interpretation. Finally, a low-T logarithmic resistance upturn is analyzed using the Lu-Shen model, supporting the presence of gapless surface states with a π Berry phase.

Keywords: topological materials, electrical transport, Lu-Shen model, quantum spin liquid

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

Abstract:

Introduction: Celiac disease (CD) and type 1 diabetes mellitus (T1D) are complex disorders with shared genetic components. The association between CD and T1D has been reported in many pediatric series. The aim of our study is to describe the epidemiological, clinical and evolutive characteristics of adult patients presenting this association. Material and Methods: This is a retrospective study including patients diagnosed with CD and T1D, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and June 2016. Results: Among 57 patients with CD, 15 patients had also T1D (26.3%). There are 11 women and 4 men with a median age of 27 years (16-48). All patients developed T1D prior to the diagnosis of CD with an average duration of 47 months between the two diagnosis (6 months-5 years). CD was revealed by recurrent abdominal pain in 11 cases, diarrhea in 10 cases, bloating in 8 cases, constipation in 6 cases and vomiting in 2 cases. Three patients presented cycle disorders with secondary amenorrhea in 2 patients. Anti-Endomysium, anti-transglutaminase and Anti-gliadin antibodies were positive respectively in 57, 54 and 11 cases. The biological tests revealed anemia in 10 cases, secondary to iron deficiency in 6 cases and folate and vitamin B12 deficiency in 4 cases, hypoalbuminaemia in 4 cases, hypocalcemia in 3 cases and hypocholesterolemia in 1 patient. Upper gastrointestinal endoscopy showed an effacement of the folds of the duodenal mucosa in 6 cases and a congestive duodenal mucosa in 3 cases. The macroscopic appearance was normal in the others cases. Microscopic examination showed an aspect of villous atrophy in 57 cases, which was partial in 10 cases and total in 47 cases. After an average follow-up of 3 years 2 months, the evolution was favorable in all patients under gluten-free diet with the necessity of less important doses of insulin in 10 patients. Conclusion: In our study, the prevalence of T1D in adult patients with CD was 26.3%. This association can be attributed to overlapping genetic HLA risk loci. In recent studies, the role of gluten as an important player in the pathogenesis of CD and T1D has been also suggested.

Keywords: celiac disease, gluten, prevalence, type 1 diabetes

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Authors: Mark E. Lokanan, Liz Lee

Abstract:

This paper aims to examine the role of accountants as gatekeepers in anti-money laundering compliance in real estate transactions. The paper seeks to answer questions on ways in which accountants are involved in real estate transactions and mandatory compliance with regulatory authorities in Canada. The data for the study came from semi-structured interviews with accountants, lawyers, and government officials. Preliminary results reveal that there is a conflict between accountants’ obligation to disclose and loyalty to their clients. Accountants often do not see why they are obligated to disclose their clients' information to government agencies. The importance of the client in terms of the amount of revenue contributed to the accounting firm also plays a significant role in accountants' reporting decision-making process. Although the involvement of accountants in real estate purchase and sale transactions is limited to lawyers or notaries, they are often involved in designing financing schemes, which may involve money laundering activities. The paper is of wider public policy interests to both accountants and regulators. It is hard not to see Chartered Professional Accountant (CPA) Canada and government regulators using the findings to better understand the decision-making processes of accountants in their reporting practices to regulatory authorities.

Keywords: money laundering, real estate, disclosure, legislation, compliance

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Authors: Ruwani N. Nugara, Masashi Inafuku, Kensaku Takara, Hironori Iwasaki, Hirosuke Oku

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Pteryxin from the partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as the active compound related to anti-obesity. Thus, in this study we investigated the mechanisms related to anti-obesity activity in-vitro. The HP was fractionated, and effect on the triglyceride (TG) content was evaluated in 3T3-L1 and HepG2 cells. Comprehensive spectroscopic analyses were used to identify the structure of the active compound. The dose dependent effect of active constituent on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis and lipogenesis (20 μg/mL) were examined in-vitro. Furthermore, higher dosage of pteryxin (50μg/mL) was tested against 20μg/mL in 3T3-L1 adipocytes. The mRNA were subjected to SOLiD next generation sequencer and the obtained data were analyzed by Ingenuity Pathway Analysis (IPA). The active constituent was identified as pteryxin, a known compound in PJT. However, its biological activities against obesity have not been reported previously. Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes and HepG2 hepatocytes (P < 0.05). Sterol regulatory element-binding protein-1 (SREBP1 c), Fatty acid synthase (FASN), and acetyl-CoA carboxylase-1 (ACC1) were downregulated in pteryxin-treated adipocytes (by 18.0, 36.1 and 38.2%; P < 0.05, respectively) and hepatocytes (by 72.3, 62.9 and 38.8%, respectively; P < 0.05) indicating its suppressive effects on fatty acid synthesis. The hormone-sensitive lipase (HSL), a lipid catabolising gene was upregulated (by 15.1%; P < 0.05) in pteryxin-treated adipocytes suggesting improved lipolysis. Concordantly, the adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was downregulated (by 42.8%; P < 0.05), further accelerating the lipolytic activity. The upregulated trend of uncoupling protein 2 (UCP2; by 77.5%; P < 0.05) reflected the improved energy expenditure due to pteryxin. The 50μg/mL dosage of pteryxin completely suppressed PPARγ, MEST, SREBP 1C, HSL, Adiponectin, Fatty Acid Binding Protein (FABP) 4, and UCP’s in 3T3-L1 adipocytes. The IPA suggested that pteryxin at 20μg/mL and 50μg/mL suppress obesity in two different pathways, whereas the WNT signaling pathway play a key role in the higher dose of pteryxin in preadipocyte stage. Pteryxin in PJT play the key role in regulating lipid metabolism related gene network and improving energy production in vitro. Thus, the results suggests pteryxin as a new natural compound to be used as an anti-obesity drug in pharmaceutical industry.

Keywords: obesity, peucedanum japonicum thunb, pteryxin, food science

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Authors: Connick K, Lalor R, Murphy A, O’Neill S. M., Rabab S. Zalat, Eman E. El Shanawany

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Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhea in human and animal populations and is an important zoonotic disease globally. In immunocompromised hosts, infection Canbe life-threatening as no effective treatments are currently available to control infection. To increase our understanding of the mechanisms that play a role in host-parasite interactions at the level of the immune response, we investigated the effects of Cryptosporidium parvum antigen (CPA) on bone marrow-derived (DCS). Herein we examined cytokine secretion and cell surface marker expression on DCs exposed to CPA. We also measured cytokine production in CD4+ cells co-cultured with CPA primed DCs in the presence of anti-CD3. CPA induced a significant increase in the production of interleukin(IL)-12p40, IL-10, IL-6, and TNF-α by DCs and enhanced the expression of the cell surface markers TLR4, CD80, CD86, and MHC11. CPA primed DC co-cultured in the presence of anti-CD3 with CD4+ T-cells inhibited the secretion of Th2 associated cytokines, notably IL-5 and IL-13, with no effects on the secretions of interferon (IFN)-γ, IL-2, IL-17, and IL-10. These findings support studies in the literature that CPA can induce the full maturation of DCs that subsequently initiate Th1 immune responses critical to the resolution of C. parvum infection.

Keywords: cryptosporidium parvum, dendritic cells, IL-12 p70, cell surface marker

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Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

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Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

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Authors: Nur Aimi Syairah Mohd Abdul Alim, Azilah Ajit, A. Z. Sulaiman

Abstract:

The present study aimed to investigate the effects of ultrasound-assisted extraction (UAE) on the extraction of Vitexin and Iso-Vitexin from Ficus deltoidea plants. In recent years, ultrasound technology has been found to be a potential herbal extraction technique. The passage of ultrasound energy in a liquid medium generates mechanical agitation and other physical effects due to acoustic cavitation. The main goal is to optimised ultrasonic-assisted extraction condition providing the highest extraction yield with the most desirable antioxidant activity and stability. Thus, a series of experiments has been developed to investigate the effect of ultrasound energy on the vegetal material and the implemented parameters by using HPLC-photodiode array detection. The influences of several experimental parameters on the ultrasonic extraction of Ficus deltoidea leaves were investigated: extraction time (1-8 h), solvent-to-water ratio (1:10 to 1:50), temperature (50–100 °C), duty cycle (10–continuous sonication) and intensity. The extracts at the optimized condition were compared with those obtained by conventional boiling extraction, in terms of bioactive constituents yield and chemical composition. The compounds of interest identified in the extracts were Vitexin and Isovitexin, which possess anti-diabetic, anti-oxidant and anti-cancer properties. Results showed that the main variables affecting the extraction process were temperature and time. Though in less extent, solvent-to-water ratio, duty cycle and intensity are also demonstrated to be important parameters. The experimental values under optimal conditions were in good consistent with the predicted values, which suggested that ultrasonic-assisted extraction (UAE) is more efficient process as compared to conventional boiling extraction. It recommended that ultrasound extraction of Ficus deltoidea plants are feasible to replace the traditional time-consuming and low efficiency preparation procedure in the future modernized and commercialized manufacture of this highly valuable herbal medicine.

Keywords: Ficus, ultrasounds, vitexin, isovitexin

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Authors: Esther Friedlander, Philip Friedlander

Abstract:

The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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