Synthetic Small Molecules Induce Insulin Secretion and Pancreatic Beta-Cell-Specific Gene Expression.

Despite various efficient pharmaceuticals which are already used to manage diabetes, new drugs are needed to preserve and restore the function of pancreatic ß-cells (pßCs) including cell-specific gene expression and insulin production and secretion. Newly developed small molecules (SMs) with potential anti-diabetic activity need to be preliminarily tested. Mice insulinoma MIN6 cells can be utilized as an in vitro screening model. These cells have pßC characteristics and can secrete insulin in response to glucose level changes. As well, the ß-cell-specific gene expression pattern of these cells is similar to that of mouse pancreatic islet cells. It is possible to use this cell line as a research tool to study the function of pßCs. To date, approximately 60 genes have been identified which are effective in the pßC embryonic development and insulin production and secretion during puberty, including pancreas/duodenum homeobox protein 1 (Pdx1), neuronal differentiation 1 (Neurod1), neurogenin3 (Ngn3), and insulin-1 precursor (Ins1). In this study, a family of new SMs that are structurally similar to glinides was synthesized through 3 different synthetic methods and categorized into 3 categories (C1-C3). Then, these novel SMs were characterized by testing their effects on cell viability, pßC-specific gene expression, and insulin secretion in MIN6 in 4 different concentrations and at 3 time points (24, 48, and 72 h). According to our results, SMs of C1 (1j, 1k, and 1l) and 2 SMs of C3 (1f, 1i), at 200 µM concentration, were able to increase the expression levels of Pdx1, Neurod1, Ngn3, and Ins1 as well as the insulin secretion after 24 h. However, C2 (1a, 1b, 1c, and 1d) did not show significant bioactivity of MIN6 cells. These investigated molecules can provide a tool for exploring pseudo-islet functionality in MIN6 cells or provide a possible basis for future therapeutic interventions for diabetes.

Clinicopathological profile of peritoneal tuberculosis and a new scoring model for predicting mortality: an international ID-IRI study.

Existing literature about peritoneal tuberculosis (TBP) is relatively insufficient. The majority of reports are from a single center and do not assess predictive factors for mortality. In this international study, we investigated the clinicopathological characteristics of a large series of patients with TBP and determined the key features associated with mortality. TBP patients detected between 2010 and 2022 in 38 medical centers in 13 countries were included in this retrospective cohort. Participating physicians filled out an online questionnaire to report study data. In this study, 208 patients with TBP were included. Mean age of TBP cases was 41.4 ± 17.5 years. One hundred six patients (50.9%) were females. Nineteen patients (9.1%) had HIV infection, 45 (21.6%) had diabetes mellitus, 30 (14.4%) had chronic renal failure, 12 (5.7%) had cirrhosis, 7 (3.3%) had malignancy, and 21 (10.1%) had a history of immunosuppressive medication use. A total of 34 (16.3%) patients died and death was attributable to TBP in all cases. A pioneer mortality predicting model was established and HIV positivity, cirrhosis, abdominal pain, weakness, nausea and vomiting, ascites, isolation of Mycobacterium tuberculosis in peritoneal biopsy samples, TB relapse, advanced age, high serum creatinine and ALT levels, and decreased duration of isoniazid use were significantly related with mortality (p < 0.05). This is the first international study on TBP and is the largest case series to date. We suggest that using the mortality predicting model will allow early identification of high-risk patients likely to die of TBP.

A case of pituitary gland abscess associated with granulomatous hypophysitis.

BACKGROUND: Granulomatous hypophysitis is a rare disease that presents with chronic inflammation of the pituitary gland. In this study, we reported a case of granulomatous hypophysitis associated with a pituitary abscess. CASE PRESENTATION: A 39-year-old woman presented with a 2-year history of infertility. For the past six months, she has suffered from amenorrhea, decreased libido, headaches, and vertigo. She was referred to our hospital with a suspected diagnosis of nonfunctioning pituitary adenoma based on her presentation and brain MRI findings. She underwent trans-sphenoidal surgery (TSS). Direct observation during surgery revealed drainage of malodor pus and pituitary gland abscess. The histopathological evaluation also showed granulomatous hypophysitis and neutrophilic microabscess formation. The patient was initially treated with high doses of ceftriaxone (2 g twice daily) and metronidazole (500 mg (mg) four times per day). Also, the patient received cortisol replacement therapy after the operation. After obtaining the antibiogram and culture results, the treatment regimen was continued for 4 weeks postoperatively, followed by amoxicillin-clavulanate (500/125 mg three times daily) for a total duration of 12 weeks. CONCLUSION: The patient recovered uneventfully and the postoperative MRI was normal without any remnant lesions.

High-power 1018 nm Yb3+ doped fiber lasers with different YDF core and coiling diameters: theoretical and experimental study.

In this paper, the effect of the active fiber's core/cladding area ratio on the output parameters of 1018 nm fiber lasers has been investigated. In this regard, we conducted a comprehensive study of two fiber lasers that utilized 25/400 and 30/250 µm ytterbium-doped fibers (YDFs), both theoretically and experimentally. The optimum length of YDFs required for 40 dB of amplified spontaneous emission suppression was calculated. Theoretical studies also identified the YDF breaking zone for lengths greater than the optimum. The experimental results showed that selecting the proper dimensions and coiling diameter for the active fiber significantly increased the power and efficiency of the YDF laser. We obtained an output power of 943 W with a 75.5% slope efficiency for the co-pumped 30/250 µm YDFL which, to the best of our knowledge, is the highest reported value for the 1018 nm co-pumped fiber laser. An analysis of the experimental and theoretical results revealed that YDFs with a core/cladding area ratio greater than 1% are more suitable for realizing a high-power 1018 nm fiber laser. The findings of this study are crucial for the development of high-power 1018 nm fiber lasers with improved performance.

Efficacy of Hemoperfusion in Severe and Critical Cases of COVID-19.

INTRODUCTION: Uncontrolled overproduction of inflammatory mediators is predominantly observed in patients with severe COVID-19. The excessive immune response gives rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients. METHOD: We conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and continuous renal replacement therapies were initiated in the hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, oxygen saturation (SPO2) at the admission, and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron© (HA330) and CytoSorb® 300. RESULT: A total of 128 COVID-19-confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission day in the control and hemoperfusion groups was 80% and 75%, respectively (p value = 0.113). The mortality rate was significantly lower in the hemoperfusion group compared to the matched group (67.3% vs. 89%; p value = 0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; p < 0.001). The median final SPO2 was statistically higher in the hemoperfusion group than in the matched group, and the median PaCO2 was lower. CONCLUSION: Among critically ill COVID-19 patients, based on our study, the use of hemoperfusion may reduce the mortality rate and improve SPO2 and PaCO2.

The Possible Role of COVID-19 in the Triggering of Underlying Mitochondrial Dysfunction in MELAS Syndrome, A Brief Report of three cases.

BACKGROUND: During corona virus pandemic, various neurological complications of COVID-19 have been reported. Recent studies demonstrated different pathophysiology for neurological manifestations of COVID-19 such as mitochondrial dysfunction and damage to cerebral vasculature. In addition, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder with a variety of neurological symptoms. In this study, we aim to assess a potential predisposition in mitochondrial dysfunction of COVID-19, leading to MELAS presentation. METHODS: We studied three previously healthy patients with the first presentation of acute stroke-like symptoms, following COVID-19 infection. We analyzed the patients' clinical data and brain magnetic resonance imaging (MRI) lesions that presented to the neurological center of a university-affiliated hospital in Tehran, Iran, from September 2020 to August 2021. RESULTS: All cases are characterized by a temporoparietal abnormality in imaging studies and electroencephalogram (EEG). Based on electrodiagnostic tests, three patients were diagnosed with myopathy. In two brothers with relatively the same symptoms, one performed muscle biopsy finding myopathic process, and genetic testing confirmed a 3243A>G point mutation in a heteroplasmic state in one of our patients. CONCLUSION: Although MELAS is not a prevalent condition, the recent increase in the number of these patients in our center might indicate the potential role of COVID-19 in triggering the silent pre- existing mitochondrial dysfunction in these patients.

One-step and sequential SARSCOV-2 polymerase chain reaction tests would not work every time.

INTRODUCTION: RT-PCR is widely used as a diagnostic test for the detection of SARS-CoV-2. In this study, we aim to describe the clinical utility of serial PCR testing in the final detection of COVID-19. METHOD: We collected multiple nasopharyngeal swab samples from patients who had negative RT-PCR test on the first day after hospitalization. RT-PCR tests were performed on the second day for all patients with initial negative result. For the patients with secondary negative results on day 2, tertiary RT-PCR tests were performed on day 3 after hospitalization. RESULT: Among 68 patients with initial negative test results, at the end of follow-up, the mortality number was 20 (29.4%). About 33.8% of patients had subsequent positive PCR test results for the second time and 17.4% of the patients who performed third PCR test had positive result. CONCLUSION: Based on this study, serial RT-PCR testing is unlikely to yield additional information.

Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19.

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.

Brucellosis in transplant recipients: A systematic review.

BACKGROUND: Brucellosis is a bacterial disease caused by Brucella species. The purpose of this study was to evaluate brucellosis in all types of transplant patients. METHODS: All the cases of brucellosis in transplant patients with no time and language limitations were searched and retrieved on May 20, 2020, using the following search keywords: (Brucella OR Brucellosis) AND (Transplant OR Transplantation) through the following medical databases: Web of Sciences, Google Scholar, Scopus, PubMed, and regional databases, for example, SID. All clinical features, including the time of transmission (before, during, and after transplantation), treatment protocols and medications, and patients' outcomes were investigated. RESULTS: A total of 14 cases reported in 14 studies (out of 777 studies) were retrieved. Kidney (50%), liver (28.5%), and hematopoietic stem cell transplantation (14.2%) were the most reported types of transplantation. The presentation of brucellosis in 42.8% of the patients occurred in the early post-transplantation period, whereas 57.1% of the cases presented with late onset disease. CONCLUSION: Brucellosis in transplant recipients seems to be uncommon even in the endemic regions. However, rare cases could be transmitted through bone marrow transplantation and transfusion. Precise screening and meticulous supervision during and after transplantation might lead to a reduction in the frequency of brucellosis.

Promising effects of atorvastatin on mortality and need for mechanical ventilation in patients with severe COVID-19; a retrospective cohort study.

PURPOSE: Considering the anti-inflammatory effect of atorvastatin and the role of medical comorbidities such as hypertension and coronary artery disease on the prognosis of the COVID-19 patients, we aimed to assess the effect of atorvastatin add-on therapy on mortality caused by COVID-19. METHODS: We conducted a retrospective cohort study, including patients who were hospitalised with confirmed diagnosis of severe COVID-19. Baseline characteristics and related clinical data of patients were recorded. Clinical outcomes consist of in-hospital mortality, need for invasive mechanical ventilation and hospital length of stay. COX regression analysis models were used to assess the association of independent factors to outcomes. RESULTS: Atorvastatin was administered for 421 of 991 patients. The mean age was 61.640 ± 17.003 years. Older age, higher prevalence of hypertension and coronary artery disease reported in patients who received atorvastatin. These patients have shorter hospital length of stay (P = .001). Based on COX proportional hazard model, in-hospital use of atorvastatin was associated with decrease in mortality (HR = 0.679, P = .005) and lower need for invasive mechanical ventilation (HR = 0.602, P = .014). CONCLUSIONS: Atorvastatin add-on therapy in patient with severe COVID-19 was associated with lower in-hospital mortality and reduced the risk of need for invasive mechanical ventilation which supports to continue the prescription of the medication.

Effect of TQM educational interventions on the management policy standard of health promoting hospitals.

The purpose of this study was to manage total quality management (TQM) to increase the standard of management policy and contribute to achieve the standards for health promotion hospitals (HPHs). This was a quasi-experimental intervention study. A total of 35 managers participated in this study were selected in the census. Based on the TQM components, educational items were provided as lectures, posters and pamphlets. The TQM questionnaire and HPHs checklist used to collect data in three different periods: before the interventions, immediately after the interventions and 3 months after the interventions (follow-up). The data analysis was done by means of SPSS software (version 23). The results showed that the average difference of the components of the qualitative groups (p < 0.001), education (p = 0.004), evaluation and feedback (p < 0.001), customer-orientation (p < 0.001), suggestion system (p = 0.024), leadership commitment (p < 0.001) was significant over the three periods. Excluding the employment status before the educational intervention (p = 0.002), there was no significant relationship between the demographic characteristics and mean score of TQM (p > 0.05). Based on the findings of this study, the educational interventions had a positive effect on quality management and management policy. Therefore, educational interventions should be accompanied by changes in the culture and management policies of the hospital to meet HPH standards.

Effect of local desmopressin administration on intraoperative blood loss and quality of the surgical field during functional endoscopic sinus surgery in patients with chronic rhinosinusitis: a triple-blinded clinical trial.

BACKGROUND: Bleeding during functional endoscopic sinus surgery always been a challenge for the quality of surgical field for surgeons. This study aimed to evaluate the effect of local nasal desmopressin premedication on blood loss and the quality of surgical field in functional endoscopic sinus surgery. METHODS: This study was conducted on 90 patients with chronic rhinosinusitis who were candidate for endoscopic sinus surgery. They were randomly assigned to two study groups. One group received a single puff of local desmopressin (10 µg) in each side of nasal cavity 30 min before the surgery and the other received normal saline instead. Blood loss and the quality surgical field were determined in 15, 30, 60 and 90 min during the surgery (scoring by BOEZAART grading system). All data were analyzed. RESULTS: Blood loss was significantly lesser in the desmopressin group (mean ± SD, 16.289 ± 5.605 ml) than in the control group (24.289 ± 5.2722 ml, P < 0.001).Surgeons were more satisfied with the surgical field in the desmopressin group than control group in all cutoff points (15, 30, 60, and 90 min during the surgery, P < 0.001). No side effects were observed using local desmopressin. CONCLUSIONS: Premedication with local desmopressin can reduce bleeding effectively and clear the surgical field during functional endoscopic sinus surgery.

Transient knockdown of Nucleoside transporter 4 gene expression as a therapeutic target in Leishmania major by antisense RNA: In vitro and in vivo studies.

BACKGROUND & OBJECTIVES: Leishmania parasites cause various clinical symptoms in humans such as cutaneous ulcers and fatal visceral diseases. These parasites cannot synthesize purine rings de novo and must uptake purines from their hosts via salvage. Salvage is regulated by permeases in the cell membrane. There are hundreds of membrane transporter proteins to receive nutrients in Leishmania. Nucleoside transporter 4 (NT4) is one of the purine transporters that is involved in enhancing the uptake of adenine in Leishmania major. They are important new drug targets for the treatment of leishmaniasis because they can be used to transport toxic purine analogs to kill parasitic cells, thus preventing the progression of the infection. The present study was conducted to silence the NT4 nucleobase involved in the salvage pathway to interrupt purine nucleotide membrane transport in the cells of L. major. METHODS: In this study, a 502 bp segment of NT4 gene sequence was selected and designed as antisense transcripts after insertion in the parasite. The NT4 construct was transfected into L. major promastigotes for in vitro study of gene expression. Then, BALB/c mice infected with transgenic Leishmania and wild-type strain along with the number and size of lesions were studied in vivo. RESULTS: The study showed that relative expression of NT4 gene in mutant Leishmania was lower than in the control on Day 3 to 20. The percentages and the number of amastigotes in infected macrophages with wild-type strain L. major were more than infected macrophages with mutant parasites. Infected BALB/c mice with transgenic Leish- mania showed a lower number and size of lesions than the BALB/c mice infected with wild-type strain. INTERPRETATION & CONCLUSION: The results of the study indicated that the use of antisense RNA reduced NT4 gene expression in L. major. Further, studies are needed to ascertain that the use of antisense can be considered as a new treatment for leishmaniasis.

A new right groin incision versus McBurney's incision for open appendectomy: a randomized controlled trial.

PURPOSE: We aimed to introduce a new surgical method for open appendectomy including a right groin incision with adipocutaneous flap and to compare its feasibility, safety, and cosmetic outcomes with classic McBurney's incision. METHODS: Patients with the diagnosis of acute appendicitis who were candidates for appendectomy surgery at General Surgery Department, Besat Hospital, Hamadan University of Medical Sciences, Iran, in 2016 and 2017, were enrolled in a randomized controlled clinical study. Patients were randomly assigned to two groups each containing 50 patients. In the case and control groups, patients underwent appendectomy using right groin incision with adipocutaneous flap and traditional McBurney's methods, respectively. RESULTS: One hundred patients with the mean age of 23.6 years (range = 4-44) old including 65 males were enrolled in the study. Patients' demographics, histopathology, and anatomical location of the appendix were not significantly different in the case and control groups. There was no significant difference in postoperative wound infection, cellulitis, hematoma, and seroma between the two groups. Patients in the case group were significantly more satisfied in terms of cosmesis than in the control group (P < .001); however, the operative time and pain were higher in the case group compared to the control group (P values = 0.016 and 0.033, respectively). CONCLUSIONS: The right groin incision for open appendectomy may be safe and feasible and the most cosmetically appealing method especially in children and patients with cosmetic concerns.

Evaluation of the Response Rates of Hospitals in the Prevention and Control of COVID-19 in Hamadan Province of Iran.

The COVID-19 pandemic has challenged the capacity of health systems in various countries. This study was designed to evaluate the response rates of hospitals in the prevention and control of COVID-19 in Hamadan province, Iran. In this cross-sectional study, all 20 hospitals in Hamadan province were monitored in February 2020. The instrument used in this study was the WHO checklist, entitled "Infection prevention and control health-care facility response for COVID-19." In each hospital, the hospital infection control officials completed the checklists under the supervision of the hospital managers and were then provided to the project manager. Data analyzed by SPSS 22 software. There were 3482 hospital beds (the average beds of each hospital was 174) in the studied hospitals. Of 15 055 patients admitted to all hospitals, 2196 (14.6%) individuals were COVID-19 patients. The total average score obtained from the checklist was 62.25. Among 7 domains studied, the lowest scores belonged to 2 domains of "infrastructure and equipment" and "patient screening and triage." The scores of domains "IPC programs" and "visitors" were significantly higher in hospitals with ICU beds than other hospitals (P-value = .03 in both domains). A comparison between university-teaching hospitals with other hospitals and those in Hamadan city with other cities revealed no significant differences in any of the domains. The mean response rate (62.25) of hospitals in terms of COVID-19 in Hamadan province indicates their relative readiness to prevent and control the COVID19 pandemic. The shortage of infrastructure and equipment and screening and triage problems of patients were the main challenges of hospitals in managing the COVID-19 pandemic in Hamadan province, Iran.

A Case of Fingolimod-associated Cryptococcal Meningitis.

BACKGROUND: Leukopenia, a rare adverse effect of Fingolimod therapy, paves the way for opportunistic infections. In this study, we reported rare fingolimod associated cryptococcal meningitis. CASE PRESENTATION: A 39-year-old woman with RRMS was referred to the emergency department. The patient's major complaints were headache, fever, weakness, and progressive loss of consciousness within the last two days prior to the referral. The patient had a history of hospitalization due to RRMS [two times]. In the second hospitalization, interferon Beta-1a was replaced with Fingolimod. Using polymerase chain reaction, Cryptococcus neoformans was detected in CSF. Liposomal amphotericin B and fluconazole [800 mg per day] were started. Six weeks later, the patient was discharged without any major complaints. CONCLUSION: Albeit fingolimod associated cryptococcal meningitis is a rare event, Fingolimod therapy in patients with MS should be performed cautiously. Regular follow-ups may give rise to a timely diagnosis of probable fingolimod associated cryptococcal meningitis. Fingolimod therapy can lead to lymphocytopenia and various infections. We, therefore, suggest that intermittent blood lymphocyte counts as well as monitoring of clinical manifestations among MS patients treated with Fingolimod to avoid additional neurological and physical disabilities in these patients.

Garcin syndrome in a case of acquired immunodeficiency syndrome.

In this study, we report a parapharyngeal diffuse large B-cell lymphoma in a human immunodeficiency virus (HIV) infected patient which had caused the patient to suffer from Garcin syndrome.

Enhancement of the Anti-biofilm Activity of Gold Nanoparticles- Itraconazole Conjugates in Resistant Candida glabrata.

INTRODUCTION: Onychomycosis, also called tinea unguium, is a common fungal infection affecting the nails. After dermatophytes, Candida species are recognized as second-line pathogens responsible for this infection. The treatment of onychomycosis requires a long time and is associated with high rates of recurrence. Antifungal medicines conjugated with gold (Au-NP) nanoparticle are the possible platforms for the reduction of drug resistance. METHODS: In the present study, we reported the in-vitro antifungal activity of itraconazole (ITZ) - Au conjugates, time-kill studies, and biofilm-producing ability of six ITZ-resistant C. glabrata. RESULTS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) quantitative results revealed that four out of six resistant isolates studied able to form biofilms in vitro. ITZ-Au conjugates were more effective than ITZ or Au nanoparticle alone, and the time-kill tests pointed to the suitable effect of ITZ-Au conjugate. CONCLUSION: The present study concluded that ITZ-Au conjugates have an inhibitory effect on the biofilm of resistant C. glabrata isolates. Further studies are needed to compare the ex-vivo onychomycosis model.

A Comparative Study on the Effect of Exosomes Secreted by Mesenchymal Stem Cells Derived from Adipose and Bone Marrow Tissues in the Treatment of Osteoarthritis-Induced Mouse Model.

BACKGROUND: Exosomes as extracellular vesicles (EVs) are nanoscale intercellular messengers secreted from cells to deliver biological signals. Today, exosomes have become a new field of research in regenerative medicine and are considered as potential therapies to control inflammation and wound healing and enhance and improve healing in many diseases. Given the global burden of osteoarthritis (OA) as the fastest-growing health condition and one of the major causes of physical disability in the aging population, research to establish EVs as therapeutic products can meet the basic clinical needs in the management of osteoarthritis and provide a therapeutic solution. OBJECTIVES: The present study is aimed at evaluating the regenerative potentials of the exosomes secreted from adipose and bone marrow tissue-derived mesenchymal stem cells (AD- and BM-MSCs) in ameliorating the symptoms of OA. METHOD: In this experimental study, AD- and BM-MSCs were isolated and cultured in the laboratory until passage 3. Finally, these cells' secreted exosomes were isolated from their conditioned medium. Ciprofloxacin-induced OA mouse models underwent intra-articular injection of exosomes from AD-MSCs and BM-MSCs. Finally, the expression levels of collagen I and II, sox9, and aggrecan genes using real-time PCR, histological analysis, and immunohistochemical (IHC) studies were performed. RESULTS: Real-time PCR data showed that although the expression level of collagen type II was lower in both exosome-treated groups than the normal, but it was significantly increased in comparison with the sham and OA, with higher expression in BM-Exo rather than AD-Exo group. Similarly, the histological staining and IHC results have provided almost identical data, emphasizing on better therapeutic effect of BM-MSCs-exosome than AD-MSCs-exosome. CONCLUSION: BM-MSCs secreted exosomes in comparison with AD-MSCs could be considered as a better therapeutic option to improve osteoarthritis and exhibit potential as a disease-modifying osteoarthritis cell-free product.

Indicators of the molecular pathogenesis of virulent Newcastle disease virus in chickens revealed by transcriptomic profiling of spleen.

Newcastle disease virus (NDV) has caused significant outbreaks in South-East Asia, particularly in Indonesia in recent years. Recently emerged genotype VII NDVs (NDV-GVII) have shifted their tropism from gastrointestinal/respiratory tropism to a lymphotropic virus, invading lymphoid organs including spleen and bursa of Fabricius to cause profound lymphoid depletion. In this study, we aimed to identify candidate genes and biological pathways that contribute to the disease caused by this velogenic NDV-GVII. A transcriptomic analysis based on RNA-Seq of spleen was performed in chickens challenged with NDV-GVII and a control group. In total, 6361 genes were differentially expressed that included 3506 up-regulated genes and 2855 down-regulated genes. Real-Time PCR of ten selected genes validated the RNA-Seq results as the correlation between them is 0.98. Functional and network analysis of Differentially Expressed Genes (DEGs) showed altered regulation of ElF2 signalling, mTOR signalling, proliferation of cells of the lymphoid system, signalling by Rho family GTPases and synaptogenesis signalling in spleen. We have also identified modified expression of IFIT5, PI3K, AGT and PLP1 genes in NDV-GVII infected chickens. Our findings in activation of autophagy-mediated cell death, lymphotropic and synaptogenesis signalling pathways provide new insights into the molecular pathogenesis of this newly emerged NDV-GVII.