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Abstract Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most common autoimmune diseases and a major contributor to patient morbidity and mortality. Although many drugs manage the disease, curative therapy remains elusive, and current treatment regimens have substantial side effects. Recently, the therapeutic potential of exosomes has been extensively studied, and novel evidence has been demonstrated. A direct relationship between exosome contents and their ability to regulate the immune system, inflammation, and angiogenesis. The unique properties of extracellular vesicles, such as biomolecule transportation, biodegradability, and stability, make exosomes a promising treatment candidate for autoimmune diseases, particularly SLE. This review summarizes the structural features of exosomes, the isolation/purification/quantification method, their origin, effect, immune regulation, a critical consideration for selecting an appropriate source, and their therapeutic mechanisms in SLE.

Abstract The current study aimed to investigate the effects of human placental mesenchymal stromal cell‐derived small extracellular vesicles (hPMSC‐sEVs) as a treatment for COVID‐19. This double‐blind, randomized, controlled clinical trial was conducted on two groups of patients with COVID‐19‐associated acute respiratory distress syndrome. After randomization, the control group received standard treatment and placebo, and the intervention arm received standard treatment plus hPMSC‐sEVs. The number of hospital deaths was considered the primary outcome. After meeting the exclusion and inclusion criteria, 21 and 24 patients were allocated to intervention and control arms, respectively. Besides admission SpO2 levels, which were significantly lower in the intervention arm (p = 0.008), all the baseline demo‐biographic and laboratory variables were similar between the groups. It was shown that hPMSC‐sEVs could significantly (p = 0.015) decrease the mortality ratio in the intervention group (4/21 [19.04%]) compared to the controls (13/24 [54.16%]). The mean time to death in the intervention and control groups was 28.06 and 11.10 days, respectively (p

Objective: Mitochondrial oxidative stress is an important factor in infertility. The mitochondrial thioredoxin systemplays an important role in this condition. N-acetyl-5-methoxy tryptamine (melatonin) plays a role in reducing oxidativestress and apoptosis in spermatogonial stem cells (SSCs). In this study, we explore the probable protective effects ofmelatonin on the mitochondrial thioredoxin system [thioredoxin 2 (Trx2)/Txnip] in SSCs under oxidative stress.Materials and Methods: In this experimental study, SSCs were co-cultured two-dimensionally (2D) with Sertoli cellsin DMEM culture medium that contained 10% fetal bovine serum (FBS), 1% antibiotics, and 10 ng/ml glial cell-derivedneurotrophic factor (GDNF) for 30 days. The cultured cells were subsequently divided into four groups: control; melatonin(250 μM, 24 hours); melatonin (250 μM, 24 hours)+hydrogen peroxide (H2O2, 50 μM, 24 hours); and H2O2 (50 μM, 24hours). Intracellular reactive oxygen species (ROS) production was determined by flow cytometry. Malondialdehyde(MDA) levels were measured by Fluorometry. The expressions of apoptotic and antioxidant genes and nuclear factorerythroid 2-related factor 2 (Nrf2), Trx2, and nicotinamide nucleotide transhydrogenase (NNT) proteins were determinedby quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Adenosine triphosphate (ATP) levelswere measured by fluorometry.Results: Melatonin reduced H2O2-induced ROS levels and apoptosis in the SSCs. Melatonin also increased mRNAexpression of Nrf2, Trx2, NNT, Sirtuin 3 (Sirt3), and decreased mRNA expression of Txnip, and increased proteinexpressions of Nrf2, Trx2, NNT thereby increasing activity of the mitochondrial thioredoxin system. In addition, melatoninincreased ATP levels.Conclusion: Melatonin increased Trx2 expression through the Nrf2 pathway. This study suggests that melatonin mayprotect SSCs from oxidative stress in diseases related to infertility.

Background: COVID-19 now is a serious concern for the world healthcare system. This study aimed to investigate possible therapeutic effect of colchicine and phenolic monoterpenes accompanied by standard care of treatment (SCT) in patients diagnosed with COVID-19. Methods: In this randomized controlled parallel clinical trial, a total number of 179 (of 200) patients with confirmed COVID-19 were enrolled according to the inclusion and exclusion criteria. The patients were allocated by simple randomization method into two groups control (receiving SCT with 71 patients) and intervention (receiving SCT plus colchicine and phenolic monoterpenes with 107 patients). The mortality ratio during hospitalization as well as a 2-week follow-up, ICU admission rate, and hospitalization duration were assessed as main outcomes. Results: The mortality ratio was 0.9% (1/108) and 8.45% (6/71) in the intervention and the control groups (p-value = 0.035) respectively, these ratios after a 14-day follow-up were 1.85% (2/108), and 9.85 (7/71) respectively (p-value = 0.031). Also, the ICU admission was significantly lower (p-value = 0.006) in the intervention group 2/108 (1.85%) compared with controls 10/71 (14.08%). Moreover, the duration of hospitalization followed a similar pattern to ICU admission with 4.17 ± 1.34 vs. 6.39 ± 2.59 days in the intervention and control groups respectively (p-value< 0.001). Furthermore, no significant side effect was found between the groups. Conclusion: According to the results, the combination of colchicine plus phenolic monoterpenes could be an additive treatment for the SCT. The authors strongly recommend further trials on this combination with other SCTs.

Breast and gynecological cancers are the most common malignancies in females. Early-stage detection and treatment could significantly reduce the mortality rate in patients. However, common treatments such as chemotherapy and radiotherapy fail after a while and lead to recurrence and drug resistance in cancer cells. The recent use of nanotechnology has enabled the development of novel approaches for diagnosing and treating oncological diseases. Chitosan-based polymer nanoparticles (CHPNPs) with unique properties such as non-toxicity, biocompatibility, and anti-carcinogenic effects are promising tools for the clinical development of targeted delivery systems. So far, various methods have been applied to use these nanoparticles in the diagnosis and treatment of various cancers. Identifying the most practical methods is one of the most important challenges in achieving effective treatments. A review of these studies can provide better horizons to realize effective treatment. In this review, we evaluate and discuss the use of CHPNPs from published literature to assess diagnostic and therapeutic strategies in breast and gynecological cancers, including ovarian and uterine neoplasms, as well as their advantages and challenges.

Objective(s): This study examined the effects of melatonin treatment on steroidogenesis dysfunction and testosterone impairment, following CoCl2-induced hypoxia in TM3 Leydig cells. Materials and Methods: The TM3 cells were divided into four groups. The first group received no treatment. The MLT group was treated with a concentration of 1 mM melatonin. In the CoCl2 group, 0.2 mM CoCl2 was added to the medium to induce Hif1α overexpression. The MLT+CoCl2 group received 0.2 mM CoCl2 and 1 mM melatonin. After 24 hr treatment, the cells and supernatants were collected and used for further determination. The MTT assay was performed to estimate the decrease in cell viability throughout the CoCl2 and melatonin treatment. The mRNA and the protein levels were evaluated using Real-time PCR and Western blot analysis. The ELISA assay kit was used to detect the testosterone content.Results: CoCl2 treatment caused Hif1α overexpression in TM3 Leydig cells. Moreover, CoCl2 treatment of these cells led to considerable downregulation of Star, Hsd3b1, and Gata4 well as Mtnr1a and Mtnr1b mRNA/protein expression coupled with testosterone content repression in the cell culture medium. Melatonin administration in CoCl2 -treated cells decreased Hif1α mRNA/protein expression, but had no significant effect on Star, Hsd3b1, Gata4, Mtnr1a mRNA/protein expression, and the testosterone level in the cell culture medium. Melatonin caused recovery of decrease in the Mtnr1b gene and protein expression. Conclusion: There was no significant effect on steroidogenesis-related genes, proteins, and testosterone synthesis in the absence of gonadotropin treatment plus melatonin following CoCl2-induced hypoxia in TM3 Leydig cells.

Abstract Objective Autophagy is an intracellular degradation pathway conserved in all eukaryotes from yeast to humans. This process plays a quality‐control role by destroying harmful cellular components under normal conditions, maintaining cell survival, and establishing cellular adaptation under stressful conditions. Hence, there are various studies indicating dysfunctional autophagy as a factor involved in the development and progression of various human diseases, including cancer. In addition, the importance of autophagy in the development of cancer has been highlighted by paradoxical roles, as a cytoprotective and cytotoxic mechanism. Despite extensive research in the field of cancer, there are many questions and challenges about the roles and effects suggested for autophagy in cancer treatment. The aim of this study was to provide an overview of the paradoxical roles of autophagy in different tumors and related cancer treatment options. Methods In this study, to find articles, a search was made in PubMed and Google scholar databases with the keywords Autophagy, Autophagy in Cancer Management, and Drug Design. Results According to the investigation, some studies suggest that several advanced cancers are dependent on autophagy for cell survival, so when cancer cells are exposed to therapy, autophagy is induced and suppresses the anti‐cancer effects of therapeutic agents and also results in cell resistance. However, enhanced autophagy from using anti‐cancer drugs causes autophagy‐mediated cell death in several cancers. Because autophagy also plays roles in both tumor suppression and promotion further research is needed to determine the precise mechanism of this process in cancer treatment. Conclusion We concluded in this article, autophagy manipulation may either promote or hinder the growth and development of cancer according to the origin of the cancer cells, the type of cancer, and the behavior of the cancer cells exposed to treatment. Thus, before starting treatment it is necessary to determine the basal levels of autophagy in various cancers.

Abstract Background Tuberculosis is a bacterial infectious disease, which affects different parts of a human body, mainly lungs and can lead to the patient’s death. The aim of this study is to investigate the global prevalence of drug-resistant tuberculosis using a systematic review and meta-analysis. Methods In this study, the PubMed, Scopus, Web of Science, Embase, ScienceDirect and Google Scholar repositories were systematically searched to find studies reporting the global prevalence of drug-resistant tuberculosis. The search did not entail a lower time limit, and articles published up until August 2022 were considered. Random effects model was used to perform the analysis. The heterogeneity of the studies was examined with the I 2 test. Data analysis was conducted within the Comprehensive Meta-Analysis software. Results In the review of 148 studies with a sample size of 318,430 people, the I 2 index showed high heterogeneity (I 2 = 99.6), and accordingly random effects method was used to analyze the results. Publication bias was also examined using the Begg and Mazumdar correlation test which indicated the existence of publication bias in the studies (P = 0.008). According to our meta-analysis, the global pooled prevalence of multi-drug resistant TB is 11.6% (95% CI: 9.1–14.5%). Conclusions The global prevalence of drug-resistant tuberculosis was found to be very high, thus health authorities should consider ways to control and manage the disease to prevent a wider spread of tuberculosis and potentially subsequent deaths.

Abstract Background Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the prevalence reported in previous studies on this type of tumor, this study was performed to determine the overall prevalence of different primary CNS tumors. Method The study was conducted as a systematic review and meta-analysis by searching international databases, including PubMed, Scopus, Science Direct, Web of science, and the Google Scholar search engine until August 2020. After transferring the studies to information management software (EndNote) and eliminating duplicate studies, the remaining studies were reviewed based on inclusion and exclusion criteria according to three stages of primary and secondary evaluation and qualitative evaluation. Comprehensive Meta-Analysis software, Begg, Mazumdar, and I2 tests were used for data analysis, publication bias analysis, and heterogeneity analysis, respectively. Results After performing the systematic review steps, 80 studies were included for final analysis. Based on 8 studies, the prevalence of brain tumors was 70.9%. Also, studies on 7 other studies showed that the prevalence of spinal tumors was 12.2%. A review of 14 studies showed that the prevalence of neuroepithelial tumors was 34.7%. The analysis of 27 studies reported a prevalence of glioma tumors of 42.8%. Analyses performed on other studies showed that the prevalence of pituitary adenomas was 12.2%, embryonal tumors 3.1%, ependymal tumors 3.2%, meningiomas 24.1%, glial tumors 0.8%, astrocytic 20.3%, oligodendroglial 3.9%, glioblastoma 17.7%, schwannoma 6.7%, medulloblastoma 7.7% and Polycystic astrocytomas 3.8%. Conclusion As a result, it can be stated that brain tumors are the most common type of primary CNS tumors. It was also observed that tumors involving neuroepithelial cells are more common in patients than other types of tumors.

Cardiovascular disease (CVD) is a major concern for health with high mortality rates around the world. CVD is often associated with partial or full occlusion of the blood vessel network. Changes in lifestyle can be useful for management early-stage disease but in the advanced stage, surgical interventions or pharmacological are needed to increase the blood flow through the affected tissue or to reduce the energy requirements. Regeneration medicine is a new science that has provided many different options for treating various diseases, especially in CVD over the years. Stem cell therapy, gene therapy, and tissue engineering are some of the powerful branches of the field that have given patients great hope in improving their condition. In this review, we attempted to examine the beneficial effects, challenges, and contradictory effects of angiogenesis in vivo, and in vitro models’ studies of CVD. We hope that this information will be able to help other researchers to design new effective structures and open new avenues for the treatment of CVD with the help of angiogenesis and regeneration medicine in the future.

Abstract Background Cancer stem cells (CSCs), subpopulations of cancer cells, are responsible for tumor progression, metastasis, and relapse. Changes in amino acid metabolism are linked to breast cancer recurrence and metastasis. Aims This study aimed to evaluate the changes in the amino acid profile in MCF‐7 and MDA‐MB‐231 cells during spheroid formation to discover the specific metabolic properties in CSCs. Methods MCF‐7 and MDA‐MB‐231 breast cancer cells were cultured as spheroids and evaluated to characterize their CSC properties. The characteristics of CSC were evaluated by examining the expression of CSC markers and conducting drug resistance assays. In addition, amino acid profile change during the enrichment of breast cancer stem cells in the spheroids was investigated by high‐performance liquid chromatography (HPLC). Results The results indicated that out of 20 different amino acids analyzed, 19 of them decreased during the spheroid formation process. Alanine, lysine, phenylalanine, threonine, and glycine showed significant reductions in the conditioned media of both cell lines in the spheroid form compared to the monolayer cells. Only one of the amino acids increased in MCF‐7 and MDA‐MB‐231 spheroids (histidine and serine, respectively). Conclusion Our results suggest that certain amino acids identified in this study can be used for a better understanding of the molecular mechanisms associated with breast cancer stem cell formation.

Tumor metabolism has provided researchers with a promising window to cancer therapy. The metabolic pathways adopted by cancer cells are different from those of normal cells. Thus, metabolism can be considered a linchpin in targeted cancer therapy. Glycolysis, pentose phosphate pathway, and mitochondria represent three critical metabolic spots with important roles in cancer cell survival and proliferation. In the present study, we aimed to target these pathways using three different inhibitors: 2-deoxyglucose, 6-aminonicotinamide, and doxycycline, separately and in combination. Accordingly, cell viability, lactate production, cell cycle profile, apoptotic profile, and expression of surface and molecular markers of MCF-7 and MDA-MB-231 breast cancer cell lines were investigated under adherent and sphere conditions. Our results from our set conditions indicated various inhibitory effects of these compounds on the breast cancer cell lines. Based on this all-around attack, the combination of drugs demonstrated the most effective inhibitory action compared to separate usage. This study suggests the combined application of these drugs in future investigations and more experimental settings in order to introduce this therapeutic strategy as an efficient anti-cancer treatment.

Abstract Background Vitiligo is a common disease with a high burden, and its recalcitrant type is unresponsive to current medical treatments. Autologous non-cultured and trypsinized melanocyte grafting, which is a simple and experience-based procedure, has been suggested for the treatment of vitiligo. Objective To assess autologous non-cultured and trypsinised melanocyte grafting in recalcitrant vitiligo. Methods This clinical trial was done on 28 patients (20 females and 8 males). After demarcation and preparation of both donor and recipient sites, both sites were shaved by a curette. The materials harvested from the donor site were trypsinized and centrifuged. The resulting suspension was mixed with hyaluronic acid gel and was spread over the shaved recipient area. Results Twenty-eight patients with a total of 108 lesions and a mean age of 25.93 ± 7.11 years were included in the present study. Generalized vitiligo (57.1%) was the most common clinical type and the face and neck regions (38%) were the most frequent treated sites. Good to excellent repigmentation was seen in the face and neck, trunk, upper extremity, and genitals in 31 (57.4%), 11 (20.4%), 9 (16.7%) and 3 (5.5%) patients, respectively. Face and neck showed significantly better results (p < 0.05). Study limitations Low sample size and single-center study. Conclusion Autologous non-cultured and trypsinized melanocyte grafting is a safe method with satisfactory outcomes in recalcitrant vitiligo. Appropriate training of physicians and proper use of specialists’ experiences can be effective in increasing the improvement rate.

Introduction: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs). Case presentation: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp. Conclusion: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.

Background and aims: The presence of an appropriate scaffold at the wound site could significantly improve the healing process. In this study, we aimed to prepare a biomimetic nanocomposite scaffold composed of chitosan, gelatin, and 58S bioglass nanoparticles for skin tissue engineering. Methods: The nanocomposite scaffolds composed of chitosan, gelatin, and 58S bioglass nanoparticles were fabricated through electrospinning process. Then the cell viability assay was performed in order to evaluate the biological properties of the membranes. The optimum concentration of bioglass nanoparticles was determined for further studies. In vitro characterization was also performed to evaluate physicochemical properties of the scaffolds. Results: The chitosan/gelatin scaffold containing 2% of 58S bioglass nanoparticles showed no cell toxicity, and the dermal fibroblasts were found capable of proliferation on the membrane. The in vitro results obtained from the scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and porosity tests demonstrated the appropriate properties of the membrane as a scaffold for skin regeneration. Conclusions: It was concluded that a chitosan-gelatin membrane containing 2% of 58S bioglass nanoparticles had the potential to function as a scaffold to accelerate wound healing due to its suitable properties, such as high porosity, high surface/volume ratio, and excellent biocompatibility.

Abstract Background MicroRNAs have short sequences of 20 ~ 25-nucleotides which are similar among family members and play crucial regulatory roles in numerous biological processes, such as in cell development, metabolism, proliferation, differentiation, and apoptosis. Results We reported a strategy for the construction of a dual-emission fluorescent sensor using carbon dots (CDs) and confirmed their applications for ratiometric microRNA-21 sensing and bioimaging of cancer cells in a microfluidic device. The composition of blue CDs (B-CDs) and yellow CDs (Y-CDs) depicts dual-emission behavior which is centered at 409 and 543 nm under an excitation wavelength of 360 nm. With increasing microRNA-21 concentration, the robust and specific binding of DNA probe functionalized B-CDs to complementary microRNA-21 target induced perturbations of probe structure and led to changing fluorescence intensity in both wavelengths. Consequently, the ratio of turn-on signal to turn-off signal is greatly altered. With monitoring of the inherent ratiometric fluorescence variation (ΔF540nm/ΔF410nm), as-prepared BY-CDs were established as an efficient platform for ratiometric fluorescent microRNA-21 sensing, with a wide linear range of 0.15 fM to 2.46 pM and a detection limit of 50 aM. Conclusions Furthermore, the proposed assay was applied for detecting microRNA-21 in dilute human serum samples with satisfactory recovery and also in MCF-7 cell lines in the range 3000 to 45,000 (cell mL−1) with a detection limit (3 cells in 10 μL), demonstrating the potential of the assay for clinic diagnosis of microRNA-associated disease. More importantly, the images revealed that MCF-7 cells well labeled with BY-CDs could exhibit the applicability of the proposed microfluidic system as an effective cell trapping device in bioimaging. Graphical Abstract

This report describes an 89-year-old woman diagnosed with Philadelphia positive Chronic Myeloid Leukemia in 2007 who was initially treated with 200 mg/day imatinib. The patient demonstrated complete molecular response (CMR) in two tests in 2015 and 2018. During treatment between 2007 and 2019, despite increased dosage of imatinib and switching her therapy to nilotinib, complete hematological response was not obtained. ARMS-PCR was performed to find the possible cause of this failed response and JAK2 V617F mutation was detected. The patient with no BCR/ABL1 transcript showed a relatively good molecular response to nilotinib, although the complete hematological response was not observed. According to our findings, tyrosine kinase inhibitor could not be an effective therapy in this JAK2 V617F-positive MPN patient with a BCR/ABL1 mutation.

Background: Interstitial lung disease (ILD) is a severe systemic sclerosis (SSc) complication with no current approved or golden standard treatment. This report aims to investigate the effectiveness of treatment with placental mesenchymal stromal cell (MSC) extracellular vesicles (EVs) in a patient with ILD due to SSc. Case presentation: The patient was a 55-year-old woman with a ten years history of SSc complicated by severe ILD. Over time, her lung disease progressed to interstitial fibrosis despite being treated with mycophenolate mofetil and monthly pulses of cyclophosphamide. Thus, she was treated with eight doses of placenta MSC-EVs. Four weeks after the third dose (Day 31 after the first dose), she reported marked improvement in her clinical symptoms, such as dyspnea and cough. Also, chest computed tomography (CT) scans demonstrated a significant reduction in ground glass consolidations and fibrotic changes. The patient was subsequently followed for twelve months, with findings showing significant improvement in exercise tolerance and reduced supplemental oxygen need. Conclusion: In this single case, placental MSC-EVs were seen to provide a potentially efficient treatment for SSc-related ILD; however, further investigation and clinical trials are necessary.

Background: Rheumatoid Arthritis patients are evaluated during treatment for various inflammatory factors such as C-reactive protein, Erythrocyte Sedimentation Rate, and Disease Activity Score, and other immune system-related factors. In the follow-up of patients with rheumatoid arthritis, hematologic factors associated with the immune system especially Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio are important. In this study, platelet to lymphocyte ratio and Neutrophil to lymphocyte ratio were compared in two groups of patients with and without ocular complications. Methods: This cross-sectional study was performed on 246 patients with rheumatoid arthritis who were referred to the rheumatology clinic of Kermanshah from December 2018 to May 2019. This study was carried out in accordance with the approval of the ethics committee (IR.KUMS.REC1397.311) at Kermanshah University of Medical Sciences. Of these patients, 191 had no ocular complications and 55 patients had ocular complications and were matched for age and sex. The blood samples were taken from patients and blood cell count was measured by Sysmex KX-21 hematology analyzer. The Spearman correlation test was used to evaluate the relationship between platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in both groups of patients without ocular complications and with ocular complications. The Disease Activity Score was compared between the two groups using the Mann-Whitney test. Results: The results of this study showed no significant difference between NLR and PLR levels in both groups of patients without ocular complications and with ocular complications. But the results showed that DAS-28 was significantly lower in the group with ocular complications (P

Abstract Background Obesity is a complex disease with an increasing prevalence worldwide. There are different weight-management options for obesity treatment, including dietary control, exercise, surgery, and medication. Medications are always associated with different responses from different people. More safety and efficacy of drugs with fewer side effects are valuable for any clinical condition. In this systematic review and network meta-analysis, different anti-obesity drugs are compared to identify the most effective drug. Methods All relevant studies were extracted by searching national and international databases of SID, MagIran, ProQuest, PubMed, Science Direct, Scopus, Web of Science (WoS), and Google Scholar without time limit until October 2020. Finally, the meta-analysis was performed with the 11 remaining studies containing 14 different drug supplements. The standardized mean difference (SMD) was calculated at a 95% confidence interval (CI) to evaluate the effects of each treatment group compared with placebo. A random-effect model was used to evaluate the effect of individual studies on the final result. Heterogeneity and incompatibility of the network were assessed by Cochran’s Q and Higgins I2, and the Net Heat chart, respectively. Data analysis was performed using R software. Results Our results showed that there were significant mean effects in people intervened with Phentermine 15.0 mg + Topiramate 92.0 mg, Phentermine 7.5 mg + Topiramate 46.0 mg, Pramlintide, Naltrexone + Bupropion 32, and Liraglutide, with SMD effects size = − 9.1, − 7.4, − 6.5, − 5.9, − 5.35, respectively. Conclusion This study was performed to compare the effect of different drugs used for weight loss in obese patients. The most effective drugs for weight loss were phentermine and topiramate, pramlintide, naltrexone, bupropion, and liraglutide compared to placebo treatment, respectively. This study provides new insights into anti-obesity drugs and hopes to shed new light on future research to manage and treat obesity.

Abstract Background Endometriosis can lead to infertility. Since there is no definitive treatment for endometriosis, animal modelling seems necessary to examine the possible treatments. Mouse endometrium cannot be separated for endometriosis induction. In addition, transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage. In this study, we defined a new model of endometriosis leading to separability of endometrium and a safe anatomical region for transplantation. Methods Forty female mice were allocated to 5 groups: 1, sham; 2, allograft uterus transplantation of mice to anterior abdominal wall of mice; 3, allograft uterus transplantation of mice to mesentery of mice; 4, xenograft endometrial transplantation of rat to anterior abdominal wall of mice; 5, xenograft endometrial transplantation of rat to mesentery of mice. Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secretion and increase endometrial thickness. Results In the 4th group of animals, compared to sham, the peritoneal concentrations of VEGF‐A, TNF‐α, NO, MDA, and serum levels of CA‐125 and IL‐37 were increased and total body weight was decreased, while weight and size of endometrial lesions were increased significantly (P

This study aimed to investigate the cytotoxicity of a probiotic mixture on human breast cancer cell lines. To prepare the mixture, local probiotic bacteria were cultured, and the lyophilized supernatant was applied for downstream experiments. The antioxidant activity, total phenol content (TPC), and fatty acid composition of the bacterial supernatant (BS) were also measured. The possible cytotoxic/anti-proliferative effect of the probiotic mixture was accessed on both breast cancer cell lines at different concentrations using MTT assay. Furthermore, the apoptosis-inducing effects of the same mixture was studied by DAPI staining. The highest level of antioxidant activity and total phenol content (TPC) were detected for the BS at 3200 µg/ml. According to the GC–MS analysis, linoleic acid (37.40 %) and oleic acid (26.93 %) were identified as the major fatty acids of the BS. The MTT assay showed that the BS has anti-proliferative effects on MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner (IC50: 3200 μg/ml). The apoptosis-inducing effects of the mixture was confirmed in both cell lines through morphological analyses of the cells’ nucleoli, and the formation of apoptotic bodies. According to these experiments, cytotoxic effects and apoptosis-inducing potential were confirmed for the BS against two human breast cancer cell lines, including MDA-MB-231, and MCF-7. Hence, it could be considered as a suitable anti-cancer agent.

Background: Despite close monitoring of transplant patients, Cytomegalovirus (CMV) infection has remained one of the most critical problems in transplantation. This study investigates the relationship between CMV viral load and clinical laboratory findings in transplant recipients. Materials And Methods: A total of 34 transplant recipients comprising 15 Kidney Transplant (KT) recipients and 19 Bone Marrow Transplant (BMT) recipients admitted to the Imam Reza Hospital in Kermanshah Province, Iran, were enrolled in this study. The CMV viral load was quantified by the real-time PCR technique. Results: The CMV viral load in KT recipients was significantly higher than in BMT recipients (P=0.03), and there was a positive association between the level of virus and the level of cyclosporine in the blood of patients (r=0.51, P=0.02). Besides, CMV viral load was positively correlated with WBC (r=0.32, P=0.04), urea (r=0.47, P=0.002), creatinine (r=0.39, P=0.01), aspartate aminotransferase (r=0.33, P=0.04), and lactate dehydrogenase (r=0.4, P=0.01). Also, it was negatively associated with albumin (r=-0.61, P

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is known to be the leading cause of chronic liver disease worldwide. This study aims to systematically review and meta-analyze the association between PNPLA3 rs738409 polymorphism and non-alcoholic fatty liver. Methods Following a systematic review and meta-analysis method, articles without any time limitation, were extracted from SID, MagIran, IranDoc, Scopus, Embase, Web of Science (WoS), PubMed and ScienceDirect international databases. Random effects model was used for analysis, and heterogeneity of studies was investigated considering the I2 index and using Comprehensive Meta-Analysis software. Results The odds ratio of CC genotype in patients with non-alcoholic fatty liver demonstrates the protective effect of CC genotype with the ratio of 0.52, whereas CG genotype presents an increasing effect of CG genotype with the ratio of 0.19, and GG genotype also showed an increasing effect of GG genotype with the ratio of 1.05. Moreover, CG + GG genotypes as a single group demostrated an odds rartio of 0.88. Conclusion This meta-analysis highlights that people with CC genotype has 52% lower chance of developing non-alcoholic fatty liver disease, and those with CG genotype had 19% higher risk of developing non-alcoholic fatty liver. Those with GG genotype were 105% more likely to develop non-alcoholic fatty liver than others. Moreover, those present in a population with CG + GG genotypes were 88% more likely to have non-alcoholic fatty liver disease.

Objective(s): This study aims to enhance 17 a-methyltestosterone loaded human serum albumin nanoparticles (MT-HSA NPs) bioavailability through a desolvation technique. Dopamine (DA) molecules were conjugated on the surface of MT-HSA NPs and have the potential to act as tiny proper ligands in a unique treatment system to cope with cancer in which drug will be transmitted to the cancer area. Herein, we used HSA as an adaptable carrier of anticancer agents for methyltestosterone transport to the tumor site via DA D1-D5 receptors. In the present study, sonication of MT-HSA solution was carried out before the desolvation procedure to increase the drug loading and entrapment efficiency. Materials and Methods: Various parameters were optimized to characterize NPs including morphology, size, zeta potential, polydispersity index, drug release profile, and entrapment efficiency. Results: Under the optimum conditions of HSA and drug (1:41), at pH 9, results demonstrate sizes of 69 nm and 82 nm for MT-HSA and MT-HSA-DA NPs respectively. For MT-HSA NPs, the polydispersity index was found to be 0.3 and the average drug loading and encapsulation efficiency were 14% and 91% respectively. Anticancer activity and the release of drug was investigated through MCF-7 breast cancer cell line. Results show that targeted NPs are more effective than non-targeted NPs. Conclusion: According to these studies, the therapeutic effects against various diseases such as cancers increase through cellular targeting property of a biocompatible drug delivery system. This is the first report for methyltestosterone delivery to breast cancer cells based on HSA NPs.

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Abstract Background Coronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease. Methods This study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I2 index in the Comprehensive Meta-Analysis software. Results The GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85. Conclusion This study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.

Type 1 diabetes (T1D) is a chronic disorder characterized by immune-mediated destruction of pancreatic insulin-producing β-cells. The primary treatment for T1D is multiple daily insulin injections to control blood sugar levels. Cell-free delivery packets with therapeutic properties, extracellular vesicles (EVs), mainly from stem cells, have recently gained considerable attention for disease treatments. EVs provide a great potential to treat T1D ascribed to their regenerative, anti-inflammatory, and immunomodulatory effects. Here, we summarize the latest EV applications for T1D treatment and highlight opportunities for further investigation.

Metabolic reprogramming is a potential hallmark of tumor cells to support continuous proliferation. Metabolic heterogeneity in breast cancer patients has been highlighted as the driving cause of tumor progression and resistance to anticancer drugs. Studying and identifying distinct metabolic alterations in breast cancer subtypes could offer new perspectives for faster diagnosis and treatment. Given cancer cell dependency on glycolysis, the primary energy source, this enzymatic pathway will play a critical role in targeting therapies. Knowledge about the specific metabolic dependencies of tumors for growth and proliferation can be promising for novel targeted and cell-based therapies. Here, the metabolic status with emphasis on glycolysis of breast cancer cell lines according to their classification was reviewed.

Abstract COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient’s death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.

Abstract Background Curcumin is herbal compound that has been shown to have anti-cancer effects in pre-clinical and clinical studies. The anti-cancer effects of curcumin include inhibiting the carcinogenesis, inhibiting angiogenesis, and inhibiting tumour growth. This study aims to determine the Clinical effects of curcumin in different types of cancers using systematic review approach. Methods A systematic review methodology is adopted for undertaking detailed analysis of the effects of curcumin in cancer therapy. The results presented in this paper is an outcome of extracting the findings of the studies selected from the articles published in international databases including SID, MagIran, IranMedex, IranDoc, Google Scholar, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant publications were selected based on the plausible keywords, in accordance with the study aims, as follows: prevalence, curcumin, clinical features, cancer. Results The results are derived based on several clinical studies on curcumin consumption with chemotherapy drugs, highlighting that curcumin increases the effectiveness of chemotherapy and radiotherapy which results in improving patient’s survival time, and increasing the expression of anti-metastatic proteins along with reducing their side effects. Conclusion The comprehensive systematic review presented in this paper confirms that curcumin reduces the side effects of chemotherapy or radiotherapy, resulting in improving patients’ quality of life. A number of studies reported that, curcumin has increased patient survival time and decreased tumor markers’ level.

Blood vessel development is one of the most prominent steps in regenerative medicine due to the restoration of blood flow to the ischemic tissues and providing the rapid vascularization in clinical-sized tissue-engineered grafts. However, currently tissue engineering technique is restricted because of the inadequate in vitro/in vivo tissue vascularization. Some challenges like as transportation in large scale, distribution of the nutrients and poor oxygen diffusion limit the progression of vessels in smaller than clinically relevant dimensions as well in vivo integration. In this regard, the scholars attempted to promote the vascularization process relied on the stem cells (SCs), growth factors as well as exosomes and interactions of biomaterials with all of them to enable the emergence of ideal microenvironment which is needed for treatment of unhealthy organs or tissue regeneration and formation of new blood vessels. Thus, in the present review we aim to describe these approaches, advances, obstacles and opportunities as well as their application in regeneration of heart as a prominent angiogenesis-dependent organ.

Background: The improvement of in vitro maturation methods, which can activate the preantral follicle growth, plays a crucial role in the production of mature oocytes in reproductive technology. Objective: To evaluate the different concentrations of 3D scaffolds of sodium alginate on hormones and gene expression in mice preantral follicles. Materials and Methods: Immature female BALB/c mice (12-14 days) were sacrificed. The follicles were removed mechanically and transferred into α minimal essential medium with 5% fetal bovine serum. The preantral follicles were incubated with different concentrations of sodium alginate (0.25%, 0.5%, and 1%) and 2D medium for 12 days. The follicles were examined for antral formation following the 10th day and the diameter on days 6 th and 12 th . The levels of hormones (AMH, androstenedione, 17 β -estradiol, and progesterone) and the expression of genes (CYP11a1, CYP17a1, CYP19a1, AMH, and GnRH) at the end of the 12 th day. Results: Maximum follicle diameter and highest percentage of antrum formation were related to 0.5% concentration (p = 0.00). The levels of hormones in different doses of sodium alginate were increased significantly compared to the control group (p = 0.00). The highest and lowest levels of these hormones were related to 0.5% concentration and 2D medium, respectively. The highest level of genes expression was observed in 0.5% sodium alginate, which showed a significant increase compared to the control group (p = 0.00). Conclusion: Proper concentration of alginate hydrogel increases follicle growth, causes follicle maturation, produces steroid hormones, and increases appropriate expression of steroidogenesis-related genes.

Angiogenesis is a strictly controlled process defined as the formation of new blood vessels essential for certain physiologic and pathologic conditions where the latter includes tumor growth, development, and metastasis. Thus, inhibiting angiogenesis along with other anticancer strategies such as chemotherapy seems to be invaluable for reaching an optimal outcome in cancer patients. It has been shown that some natural plant-derived compounds are capable of preventing the formation of these new blood vessels in the tumor and also inhibit the proliferation and growth of the cancer cells. In this review, we intend to introduce plants with anti-angiogenic properties and discuss their related features.

Background: Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol. Objective: To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L. (TT) on the proteome and expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the human umbilical vein endothelial cells (HUVEC) and human bone marrow endothelial cell (HBMEC) lines. Methods: Two cell lines were cultured and induced with lipopolysaccharide (LPS). The primed cells were then treated with aqueous extract and saponin fraction of TT. The protein profile of the endothelial cells was assessed under normal and LPS-induced conditions using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 2D gel electrophoresis (2-DE). The levels of VCAM-1, ICAM-1, and E-selectin were estimated by use of western blotting. Results: LPS-induced HUVECs and HBMECs were shown to significantly increase the expression of ICAM-1, VCAM-1, and E-selectin in comparison to control groups. Our findings revealed that TT extract resulted in significantly more reduced levels of proteom (80 spots) as well as all the three mentioned proteins compared with the effect of saponin fraction alone. Conclusion: TT extract and its saponin fraction exerted anti-inflammatory effects on HUVEC and HBMEC lines and reduced the expression of ICAM-1, VCAM-1, and E-selectin. However, the anti-inflammatory effect of aqueous extract was greater than that of saponin fraction. Therefore, TT could be considered as a potential candidate for the treatment or prevention of atherosclerosis.

Recent advances in nanotechnology sciences lead to the development of new treatment approaches for various diseases such as cancer. Nanotechnology advances can potentially minimize the side effects of drugs through the employment of effective and controlled drug delivery systems (DDSs). Polymers are optimal tools providing drug delivery mechanisms through the unique features of pharmacokinetics, circulation time, biocompatibility, and biodegradability. This systematic review aimed to evaluate polymer-based DDSs for anticancer drugs and their various therapeutic applications in cancer treatment. This study was conducted with no time limitation by November 2021. Related articles were collected through a deep search in English and Persian databases of SID, MagIran, Scopus, Web Of Science (WoS), PubMed, Science Direct, and Google Scholar. Keywords included drug delivery system, anticancer agent, polymeric nanostructure-based drug delivery, polymer-based drug delivery, and polymeric system. As the results showed, polymeric nanoparticles (PNPs) have influential roles in cancer treatment than conventional chemotherapy procedures. PNPs can reduce cytotoxicity following chemotherapy drug administration, improve the solubility characteristics of these therapeutic agents and inhibit the rate of tumor growth.

COVID-19 affects several human genes, each with its own p-value. The combination of drugs associated with these genes with small p-values may lead to an estimation of the combined p-value between COVID-19 and some drug combinations, thereby increasing the effectiveness of these combinations in defeating the disease. Based on human genes, we introduced a new machine learning method that offers an effective drug combination with low combined p-values between them and COVID-19. This study follows an improved approach to systematic reviews, called the Systematic Review and Artificial Intelligence Network Meta-Analysis (RAIN), registered within PROSPERO (CRD42021256797), in which, the PRISMA criterion is still considered. Drugs used in the treatment of COVID-19 were searched in the databases of ScienceDirect, Web of Science (WoS), ProQuest, Embase, Medline (PubMed), and Scopus. In addition, using artificial intelligence and the measurement of the p-value between human genes affected by COVID-19 and drugs that have been suggested by clinical experts, and reported within the identified research papers, suitable drug combinations are proposed for the treatment of COVID-19. During the systematic review process, 39 studies were selected. Our analysis shows that most of the reported drugs, such as azithromycin and hydroxyl-chloroquine on their own, do not have much of an effect on the recovery of COVID-19 patients. Based on the result of the new artificial intelligence, on the other hand, at a significance level of less than 0.05, the combination of the two drugs therapeutic corticosteroid + camostat with a significance level of 0.02, remdesivir + azithromycin with a significance level of 0.03, and interleukin 1 receptor antagonist protein + camostat with a significance level 0.02 are considered far more effective for the treatment of COVID-19 and are therefore recommended. Additionally, at a significance level of less than 0.01, the combination of interleukin 1 receptor antagonist protein + camostat + azithromycin + tocilizumab + oseltamivir with a significance level of 0.006, and the combination of interleukin 1 receptor antagonist protein + camostat + chloroquine + favipiravir + tocilizumab7 with corticosteroid + camostat + oseltamivir + remdesivir + tocilizumab at a significant level of 0.009 are effective in the treatment of patients with COVID-19 and are also recommended. The results of this study provide sets of effective drug combinations for the treatment of patients with COVID-19. In addition, the new artificial intelligence used in the RAIN method could provide a forward-looking approach to clinical trial studies, which could also be used effectively in the treatment of diseases such as cancer.

Tumor angiogenesis plays a vital role in tumor growth and metastasis. It is proven that in tumor vasculature, endothelial cells (ECs) originate from a small population of cancer cells introduced as cancer stem cells (CSCs). Autophagy has a vital role in ECs differentiation from CSCs and tumor angiogenesis. High levels of reactive oxygen species (ROS) increased autophagy by inhibition of glucose-6-phosphate dehydrogenase (G6PD) and inactivation of the pentose phosphate pathway (PPP). Previously, we suggested that cancer cells initially increase the glycolysis rate when encountering ROS, then the metabolic balance is changed from glycolysis to PPP, following the continuation of oxidative stress. In this study, we investigate the possible role of persistent oxidative stress in the differentiation of CSCs into tumor ECs by relying on the relationship between the ROS, PPP and autophagy. Because tumor angiogenesis plays an important role in the growth and development of cancer, understanding the mechanisms involved in differentiating ECs from CSCs can help find promising treatments for cancer.

Objective(s): Nanocarriers are drug delivery vehicles, which have attracted the attention of researchers in recent years, particularly in cancer treatment. The encapsulation of anticancer drugs using protein nanocages is considered to be an optimal approach to reducing drug side-effects and increasing the bioavailability of anticancer drugs. Epirubicin (EPR) is an active chemotherapeutic medication used in the treatment of breast cancer. However, the toxicity of this drug against normal cells is a considerable limitation in therapy. EPR toxicity could be reduced using nanocarriers and dual-targeted drug delivery. Dual-targeted drug delivery system was developed by the conjugation of dopamine (DA) with horse spleen apoferritin (HsAFr)-encapsulated EPR to overcome the limitations of chemotherapeutic EPR in breast cancer treatment. HsAFr-EPR-DA complexes could target the scavenger receptors, transferrin receptors 1, and DA receptors, which are overexpressed on breast cancer cells. Materials and Methods: UV-Visible, fluorescence, and circular dichroism (CD) spectroscopic techniques and transmission electronic microscope (TEM) have been applied to characterize HsAFr-EPR-DA complexes. In the present study, we utilized human breast cancer cell line (MCF-7), aiming to compare the cytotoxicity of HsAFr-EPR-DA complexes to free EPR. Results: The toxicity was measured using the MTT assay, which demonstrated that the dual-targeted nanocarrier (HsAFr-EPR-DA) enhanced cytotoxicity against MCF-7 more significantly compared to non-targeted nanocarriers.Conclusion: The findings of the current research indicated that the synthesized HsAFr-DA complex was an optimal nanocarrier for the dual-targeted delivery of anticancer drugs.

Abstract Background Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions. Main body While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells. Conclusion Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches.

Introduction: There are controversial reports about association between sleep and Hypothalamic-Pituitary-Adrenal (HPA) activity. Studies have reported the influence of insomnia on HPA hormones. However, they usually ignored the heterogeneity of insomnia symptoms, so subtypes of the disorder have not been considered in the reports. The present study aimed to investigate the final and intermediate products of HPA system among a group of psychophysiological and paradoxical insomniac patients in comparison to a group of normal sleepers. Methods: We investigated the awakening serum level of Adrenocorticotropic Hormone (ACTH) and cortisol after one night Polysomnography (PSG) in 17 subjects with psychophysiological insomnia, 19 subjects with paradoxical insomnia and 17 subjects with normal sleep profile. Groups were matched for age and Body Mass Index (BMI). Serum levels of ACTH and cortisol were measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Results: Although, a tendency toward elevation of both ACTH and cortisol was observed among patients with paradoxical insomnia compared to both control and psychophysiological insomnia, the differences were not significant comparing three groups. According to regression analysis, higher Non-Rapid Eye Movement sleep (NREM) arousal and Pulse Transit Time (PTT) significantly predicted higher level of ACTH. Conclusion: These findings could suggest the personality traits hypothesis for paradoxical insomnia. Both cortical and subcortical arousal could lead to more HPA activity and higher ACTH level. Further studies are recommended to confirm the hypothesis.

As a process entailing a high turnover of the host cell molecules, viral replication is required for a successful viral infection and requests virus capacity to acquire the macromolecules required for its propagation. To this end, viruses have adopted several strategies to harness cellular metabolism in accordance with their specific demands. Most viruses upregulate specific cellular anabolic pathways and are largely dependent on such alterations. RNA viruses, for example, upregulate both glycolysisand glycogenolysis providing TCA cycle intermediates essential for anabolic lipogenesis. Also, these infections usually induce the PPP, leading to increased nucleotide levels supporting viral replication. SARS-CoV-2 (the cause of COVID-19)that has so far spread from China throughout the world is also an RNA virus. Owing to the more metabolic plasticity of uninfected cells, a promising approach for specific antiviral therapy, which has drawn a lot of attention in the recent years,would be the targeting of metabolic changes induced by viruses. In the current review, we first summarize some of virus-induced metabolic adaptations and then based on these information as well as SARS-CoV-2 pathogenesis, propose a potential therapeutic modality for this calamitous world-spreading virus with the hope of employing this strategy for near-future clinical application.

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells’ bioenergetics differently. Tumor cells’ dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.

Background and Aim: Human papillomavirus (HPV) infection is a prevalent, life-threatening disease and cause of cancer among women. Therefore, in recent years, developing novel anti-HPV agents is highly regarded. The study was planned to bioinformatic screening for E1 and E2 potential inhibitors of HPV serotypes including 16,18,31,33 and 45 types from medicinal plants. Materials and Methods: This is a descriptive-analytic study. In the first step, three-dimension structure of phytochemicals were retrieved from PubChem database and then the cell cytotoxicity and mutagenesis potential of them were evaluated. In the next step, the amino acid sequences of two key proteins of mentioned types of HPV including E1 and E2 were obtained from Uniprot database. Furthermore, the conserved and variable regions of the protein sequences were predicted using multiple sequence alignment method. Finally, the three-dimension structure of mentioned proteins was determined by homology modeling method and potential interactions of the phytochemicals with the proteins were investigated using molecular docking method through Autodock 4.2.6 software. Findings: The results demonstrated that ursolic acid has no cytotoxicity and mutagenesis potential with appropriate physicochemical properties. Results also showed that mentioned compound had strong interaction with both E1 and E2 of all studied serotypes. Furthermore, the evaluation of ursolic acid and E1 and E2 interactions showed that amino acid is involved in conserved regions of mentioned serotypes. Conclusion: Based on the obtained results of present study ursolic acid could be good candidate for more in vitro and in vivo studies of its anti HPV activity.

Introduction: Date palm pollen (DPP) is the male reproductive soft powder from date flowers widely used as the valuable dietary supplement to fortify the size of testis and ovarian to increase the power of sex. This part of date palm significantly exhibited anti-diabetic, anti-inflammation and protective effects against male and female infertility. Though the anticancer activity of date fruits was previously reported, the DPP anti-angiogenic effects were not reported, and as the first study, its inhibitory effects were examined in the current study. Methods: The DPP soft powder was collected to prepare its hydro-alcoholic extract to examine its anti-angiogenic activity in an in vitro model. At different concentrations, the cytotoxicity of the prepared extract was examined on human umbilical vein endothelial cells (HUVECs) using lactate dehydrogenase method. Cell proliferation was determined using the MTT assay and cytodex-3D model in collagen gel was used to assay its possible anti-angiogenic activity. The expression of VEGF, MMP-2 and MMP-9 genes was measured using real-time polymerase chain reaction (PCR). Finally, molecular docking simulation was used to highlight the possible role of DPP polyphenols to interact with the associated receptors. Results: The prepared hydro-alcoholic extract exhibited significant anti-angiogenic activity in a dose-dependent manner and decreased the endothelial cell proliferation. The calculated IC50 value for the examined extract in angiogenesis model was 260 µg·mL, respectively. Also, the expression of VEGF, MMP-2 and MMP-9 genes were significantly decreased. Docking simulation results unveiled that the isolated DPP polyphenols have the affinity to interact with ctDNA, VEGF and its receptors. Conclusion: The DPP is the new source of non-toxic anti-cancer agents to use as a dietary supplement in the pre-treatment of cancer.

Polymorphism in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence warfarin dose requirement since patients with CYP2C9*2, CYP2C9*3 and VKORC1 mutant alleles require lower warfarin maintenance doses. Studies have reported the ethnic variations in the frequency of these genes within the various populations in Iran and other parts of the world. However, no such study has been done yet on Kurdish population in Kermanshah. From Kurdish population of Kermanshah province in Iran, a total of 110 patients who had heart surgery and taking warfarin, were genotyped for polymorphisms of VKORC1-1639 G>A, CYP2C9*2, and CYP2C9*3. Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of MspI, AVAII and KpnI, respectively. The frequencies of VKORC1-1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for CYP2C9 1*/1*, 1*/2*, 2*/2*, 1*/3*, 3*/3*, 2*/3* were 71%, 17%, 5.4%, 1.8%, 4.5%, and 0%, respectively. The frequency of VKORC1-1639A allele was 42.3% and the frequencies of CYP2C9*2 and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of CYP2C9 and VKORC1-1639 variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.

The present study investigated the radioprotective efficacy of lentil (Lens culinaris) sprouts against X-ray radiation-induced cellular damage. Lentil seeds were dark germinated at low temperature and the sprout extract was prepared in PBS. Free radical scavenging of extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and then the radioprotective potency of extract (0 to 1000 μg/mL) on the lymphocyte cells was determined by lactate dehydrogenases assay. Moreover, micronuclei assay was assessed using the cytokinesis-block technique. The irradiations were performed using 6 MV X-ray beam. The value of IC 50 for DPPH assay was 250 μg/mL. The median lethal dose for radiation was determinate at 5.37 Gy. Pretreatment with lentil sprout extract at 1000 μg/mL reduced cytotoxicity at 6 Gy total concentration from 70% to 50%. The results of micronuclei assay indicated that cells were resistant to radiation at concentrations of 500-1000 μg/mL of exogenous lentil sprout extract. The value of median effective concentration for micronuclei assay was 500 μg/mL. The results indicated that lentil sprout extract showed actually somewhat radioprotective effect on lymphocyte cell. In addition, the obtained results suggest that extract of total lentil sprout have more antioxidant activity than radicle part.

Cancer cells can adapt to low energy sources in the face of ATP depletion as well as to their high levels of ROS by altering their metabolism and energy production networks which might also have a role in determining cell fate and developing drug resistance. Cancer cells are generally characterized by increased glycolysis. This is while; cancer stem cells (CSCs) exhibit an enhanced pentose phosphate pathway (PPP) metabolism. Based on the current literature, we suggest that cancer cells when encountering ROS, first increase the glycolysis rate and then following the continuation of oxidative stress, the metabolic balance is skewed from glycolysis to PPP. Therefore, we hypothesize in this review that in cancer cells this metabolic deviation during persistent oxidative stress might be a sign of cancer cells’ shift towards CSCs, an issue that might be pivotal in more effective targeting of cancer cells and CSCs.