Archives of Razi Institute最新文献

Diabetes mellitus (DM) is a prevalent cause of platelet (PLT) activation. Inflammation-induced dysregulation of PLT function adds to chronic complications. Ras-related C3 botulinum toxin substrate 1 (Rac1), a 21 kDa G-protein, has been shown to modulate many PLT activities. We hypothesized that Rac1 may influence the PLT release of CXCL4 and CCL5, thereby contributing to macrovascular and microvascular problems in DM. The study included Swiss albino male mice pretreated with the Rac1 inhibitor NSC23766 and streptozotocin (STZ) to induce diabetes. A sample of 150 diabetic patients and 50 healthy controls was also analyzed. Statistical analyses were performed using Mann-Whitney tests on one hundred fifty confirmed diabetic patients who visit Layla Qasim health center for diabetes management, and 50 healthy individuals were included in this study. The serum CXCL4 and CCL5 in diabetic patients and healthy volunteer were measured. Swiss albino male mice received pretreatment of 5 mg/kg of the Rac1 inhibitor NSC23766, followed by injection of streptozotocin at a dosage of 45 mg/kg body weight, twice daily for five days. Rac1 activity in the PLT was measured using pulldown assay and Western blot method. Blood chemokine concentrations were also assessed using ELISA, and histological scores for the kidney, liver, pancreas, and lung were evaluated. CXCL4 and CCL5 levels were markedly elevated in DM patients compared to healthy individuals. Our findings indicated that streptozotocin induced diabetes mellitus in mice. GTP-Rac1 was induced in diabetic mice, and pretreatment with NSC23766 was significantly lower compared to vehicle group. Furthermore, diabetic mice showed significantly greater levels of CXCL4 and CCL5 (P <0.05) compared to the sham group. CXCL4 levels were reduced by 80% following Rac1 inhibition (P <0.05), while CCL5 levels decreased by 55.5% (P <0.05). The current study indicates that Rac1 plays a pivotal role in releasing PLT chemokines due to diabetes-induced inflammation in several organs, and inhibiting Rac1 may represent a novel therapeutic approach to managing inflammation in diabetic individuals.

The ongoing occurrence of zoonotic and viral diseases, such as SARS-CoV-2, H5N1, Nipah, and Ebola viruses, underscores the requirement for transformative innovations in vaccine and antiviral development. Classic vaccine technologies like inactivated or live-attenuated virus products have lengthy production cycles, cold-chain storage, and are poorly suited to reacting rapidly to emerging threats This review synthesizes the most recent advances in molecular virology, immunogen design, and biotechnology that will propel the next generation of prevention and treatment tools. We begin with the genomic and structural characteristics of high-consequence zoonotic viruses, highlighting the molecular determinants for virulence, host switching, and immune evasion. The review then provides a comparative review of the emerging vaccine platforms such as mRNA, DNA, viral vector, subunit, and inactivated vaccines based on design rationale, delivery systems, immunogenicity profiles, and global rollouts. At the same time, molecular mechanisms of antiviral drugs acting against viral polymerases, proteases, and entry mechanisms are discussed, and the new challenge of resistance evolution is emphasized. We also highlight recently developed molecular diagnostic tools like CRISPR-based tools, nanopore sequencing, and isothermal amplification technologies that are transforming real-time pathogen diagnosis in veterinary and human medicine. Last, the One Health aspect is introduced through veterinary applications of vaccines to zoonotic spillover prevention and antimicrobial resistance. In conclusion, this review gives a vision-orientated account of molecular strategies that bring together human and animal medicine to combat future pandemics. Our aggregated tables and visualizations are an asset for researchers, clinicians, and policymakers interested in the improvement of epidemic preparedness and cross-species disease surveillance.

Acalypha paniculata (AP) is a subshrub traditionally used in ethnomedicine for treating skin diseases, asthma, and inflammatory conditions. This study focuses on the eco-friendly synthesis and characterization of silver nanoparticles derived from the Acalypha paniculata herb. The safety profile of Acalypha paniculata-based silver nanoparticles (APSN), particularly regarding behavioral, biochemical, and histopathological aspects, has not been thoroughly investigated. This study evaluated the acute and sub-acute toxicity of APSN in rats, adhering to OECD guidelines. Four groups of six rats each received a single oral dose of APSN at 500, 1000, and 2000 mg/kg. Post-administration, the rats were monitored for thirteen signs of general toxicity over four hours and assessed for motor and locomotive behavior using a rota rod and open field test on the 14^th day. In repeated- dose toxicity studies, four groups of six rats each were administered 500, 1000, and 2000 mg/kg APSN daily for 28 days. Parameters such as feed intake, body weight, biochemical and hematological profiles, and organ histopathology were studied. The results of the acute toxicity studies indicated no evident signs of toxicity, including abnormal motor locomotion and behavior. The rats exhibited good tolerance across the three doses. However, sub-acute exposure at 2g/kg showed minor morphological changes in liver histopathology, evidenced by minimal hepatic cell infiltration. The oral no-observed-adverse-effect-level (NOAEL) exceeded 2000 mg/kg/day in both male and female Wistar rats, confirming the safety of APSN when administered orally. This study supports the ethnomedicinal claim of APSN, though further clinical studies are necessary to confirm these findings and ensure comprehensive safety validation.

SARS-CoV-2, the virus responsible for COVID-19, is characterized by its high transmission rate, leading to a global pandemic. Millions of people have lost their lives due to the infection caused by this virus. The ability of the virus to spread rapidly and infect large numbers of people has highlighted the need to understand its mechanisms of infection. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for SARS-CoV-2 cell entry. SARS-CoV-2 exhibits a high affinity to this receptor and shows high infectivity, leading to an explosive increase in patients infected with COVID-19. ACE2 is the carboxypeptidase homolog of ACE, which produces angiotensin II, the main active peptide of the renin-angiotensin system. From a pathophysiological perspective, this system regulates vital processes across different organs. Additionally, ACE2 enzyme activity could play a protective role against acute respiratory distress syndrome (ARDS) caused by viral pneumonia. Upon infection, SARS-CoV-2 downregulates the expression of ACE2, which is possibly related to the pathogenesis of ARDS. Since this receptor is present in various other tissues such as the heart, kidney, gastrointestinal tract, reproductive system, and sensory organs, it may contribute to pathological symptoms in these organs. Thus, ACE2 is not only a receptor for SARS-CoV-2 but may also play a crucial role in various aspects of the pathogenesis of COVID-19 and potential post-COVID-19 syndromes. Administering ACE2 could competitively bind to SARS-CoV, thereby reducing viral spike protein from attaching to transmembrane ACE2 and consequently reducing viral cell entry into cells and COVID-19 symptoms. In this review, we first examine the role of ACE2 in the pathophysiology of SARS-CoV-2 across different tissues and propose treatment strategies for COVID-19 that involve ACE2.

Gastrointestinal (GI) cancers are among the most common and fatal tumors worldwide, with incidence rates varying significantly due to factors such as inheritance, lifestyle, and diet. Understanding the prevalence and related risk factors is essential for improved prevention and treatment techniques. Data were collected from patients admitted to Baqaei Hospital during 2019 to 2022. The questionnaire includeddemographic data (age and sex), occupation, location of malignancy, genetic history, smoking habits, underlying disease (hypertension, diabetes, rheumatism), performing physical activities (exercise), presence of metastasis ,and complete survival status. The data analysis of this study was performed using statistical software: SPSS. Both linear regression and unadjusted logistic regression analyses were conducted. T-test and chi-square statistical methods were also used for analysis in this study. The results revealed that the survival rate in patients with gastrointestinal malignancies are significantly associated with factors such as age, family history, tumor location (colon and pancreas), history of smoking, concomitant disease, metastasis (rectal cancer), and physical activity. The average age of death is 66.05 years. Among them, approximately 20.4% had a family history of cancer. Also, 50% exhibited metastasis, 44.8% had a history of smoking, 74.8% had underlying diseases, and 99.6% had not exercised. Physical activity was significantly lower in deceased patients, and fewer deaths occurred among those with high physical activity levels. Rectal cancer had the highest percentage of metastasis among living and deceased patients. It will be useful to carry out more studies to determine the clinical and demographic factors that affect the survival of patients with colorectal cancer patients. Public awareness and early medical consultation are crucial for improving outcomes.

Antibiotic resistance (AR) has become a significant worldwide public health concern in the twenty-first century. Antimicrobial resistance (AMR) occurs when microorganisms, such as bacteria, fungi, parasites, and viruses acquire genetic changes that make them resistant to antimicrobial drugs, including antibiotics. AMR, often known as the "Silent Pandemic," requires prompt and persistent intervention rather than postponement. Failure to take preventative measures will result in AMR becoming the primary cause of mortality worldwide. In the fight against multidrug-resistant bacteria to halt antibiotic resistance, conventional techniques for developing drugs are expensive and time-consuming. However, AI systems can rapidly scan extensive chemical libraries and forecast possible antibacterial agents. Considering the slow progress of ongoing antibiotic research, it is essential to accelerate the development of novel antibiotics and supplementary treatments. The acceleration is essential to effectively address the increasing health risk posed by antibiotic-resistant bacteria and to ensure that we maintain an advantage in combating these emerging threats. The use of AI in medical research holds significant promise, particularly in addressing multidrug-resistant (MDR) infections to battle AMR. This study focuses on the effective applications of AI in addressing AMR and its potential benefits for humanity. It covers fundamental concepts of AI, current available resources for AI, its uses and scope, as well as its benefits and limitations.AI algorithms consistently observe antibiotic usage, diseases occurrences, and resistance trends. This review explores how AI is used to identify AMR markers, diagnose AMR, develop smallmolecule antibiotic and also emphasizes emerging research domains, such as AMR detection and novel medication development, which contribute to managing AMR.

Neospora caninum plays a significant role in causing abortion and reproductive failure in dairy cattle. The majority of neosporosis-related abortions occur during the 5-6 months of gestation. Outcomes can include fetal death within the uterus, resorption, mummification, autolysis, stillbirth, birth with clinical symptoms, or birth of clinically healthy but chronically infected ones. The objective of this study was to identify N. caninum infection in aborted bovine fetuses through molecular analysis and mouse bioassay testing. From 2019 to 2022, a total of 121 bovine aborted fetuses were collected from dairy farms in Khorasan Razavi province. Fetal brain samples were screened for detection of the parasite DNA using polymerase chain reaction assay (PCR). Additionally, a portion of PCR-positive brain tissue was homogenized and inoculated into the peritoneum of five BALB/c mice. All mice were sacrificed six weeks post -infection and examined using serology, microscopy and PCR methods. If the mice's brain samples tested PCR -positive, the mouse bioassay test was repeated two times. The N. caninum DNA was detected in 19.8% of brain samples in bovine aborted fetuses. Among PCR-positive brain samples, only ten samples were suitable for mouse bioassay examination. All inoculated mice remained seronegative and showed no clinical signs after three rounds of bioassays, although PCR testing of the brain samples of three mice groups were PCR-positive after repeated bioassays. The PCR results showed a moderate frequency of N.caninum infection in aborted bovine fetuses. Furthermore, the isolates obtained in this study demonstrated low pathogenicity in BALB/c mice, suggesting that they belong to an avirulent strain.

The Coronavirus disease 2019 (COVID-19) spread all over the world and was accepted as a pandemic by the World Health Organization (WHO) on March 11, 2020. Lungs are predominantly affected by tuberculosis and COVID -19. The objective of the study was to assess the clinical features of COVID-19 in active tuberculosis (pulmonary and extra-pulmonary) and to identify the radiological and laboratory picture of COVID -19 in patients with active tuberculosis. A cross -sectional study was conducted by the Department of Respiratory Medicine, Himalayan Institute of Medical Sciences, among patients of active tuberculosis (pulmonary and extra-pulmonary) who presented to the General Outpatient Department (OPD) of the Respiratory Medicine Department. The questionnaire included questions on socio -demographic profile, clinical features, comorbidities, clinical history, any substance abuse and laboratory investigations. Data was analyzed by SPSS software version 21.0, while Chi-square test was used for categorical data analysis. The mean age of the study participants was 47.5±5.3 years (Range 18-72). Males constituted the larger group (59.38%) as compared to females (40.63%). The prevalence of COVID-19/tuberculosis co-infection in the present study was 21.8%. Positive history of contact, bacterial culture, PCR, and CBNAAT, use of the drug, presence of cavity and pleural effusion on X -Ray, showed all remarkably higher chances (p< 0.05) of developing co-infection. The prevalence of COVID-19/tuberculosis co-infection in the present study was high. Significantly associated factors can help in identifying COVID -19 infection among tuberculosis patients. Therefore, it is recommended that screening for these factors should be done for all tuberculosis patients coming for treatment and Covid 19 vaccination.

Ascites, the pathological accumulation of fluid within the peritoneal cavity, often results from an imbalance between fluid production and absorption. This case involved a seven-and-a-half-year-old neutered female Labrador retriever presenting with abdominal distension, inappetence, weakness, and lethargy. Clinical examination revealed respiratory distress, abdominal pain, pale mucous membranes, muffled heart sounds, and a positive fluid thrill upon abdominal palpation. Hematological evaluation showed normocytic normochromic anemia, neutrophilia, leukocytosis, and thrombocytopenia. Biochemical analysis revealed hypoalbuminemia, hypoglycemia, elevated liver enzymes (ALT, AST, ALP), and increased blood urea nitrogen (BUN) and creatinine levels, indicating impaired liver and kidney function. Arterial blood gas analysis indicated hepatobiliary dysfunction, showing low pCO₂, reduced bicarbonate (HCO₃) levels, and a negative base excess (BE), consistent with metabolic acidosis with compensatory respiratory alkalosis. Radiographic imaging showed a ground-glass appearance and pleural effusion, while ultrasonography confirmed the presence of free anechoic fluid in the peritoneal cavity, rounded liver margins, a dilated hepatic portal vein, hyperechoic liver parenchyma, ill-defined corticomedullary junctions in the kidneys, and splenomegaly. Cytological analysis of the straw-colored ascitic fluid showed fibrin strands and white blood cells. The serum-ascites albumin gradient (SAAG) was 2.4 g/dL, indicating portal hypertension as the underlying cause. The final diagnosis was ascites of hepatic origin. Treatment included diuretics, antibiotics, fluid therapy, liver supplements, and dietary modifications, including salt restriction and the provision of high-quality protein. This case underscores the importance of a comprehensive diagnostic approach that combines clinical, hematological, biochemical, and imaging findings to enable timely intervention and effective management of canine ascites.

Colitis-associated colorectal cancer (CAC) is a serious condition driven by chronic inflammation in the colon, representing a significant challenge in both preventative and therapeutic contexts. Apis mellifera intermissa venom has shown promising therapeutic potential in various disease models, particularly those involving inflammation and tumorigenesis. This study evaluates the therapeutic effects of venom derived from honeybees native to Algeria on the progression of CAC in azoxymethane (AOM)-treated mice. A total of 28 male mice were randomly allocated into four groups (n=7 per group): a control group received a tap drinking water, an AOM group (10 mg AOM /kg body weight), a bee venom group (0.76 mg/kg body weight), and a combined bee venom + AOM group. CAC was induced in mice by a single intraperitoneal injection (i.p) of AOM, and a high-fat diet (45% fat by diet weight) for two weeks. The potential therapeutic effect was evaluated by administering bee venom intraperitoneally on a daily basis for two weeks. AOM significantly reduced body weight, food and water intake while increasing colon weight. Hematological analysis revealed significant reductions in red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT), coupled with increased white blood cell counts, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Elevated serum C-reactive protein (CRP) levels further confirmed systemic inflammation. Macroscopic examination and histopathological analyses of the colon revealed extensive pathological changes in the AOM group, including severe mucosal inflammation, necrotic epithelial damage, and substantial immune cell infiltration. Noteworthy, co-treatment with bee venom effectively mitigated these pathological alterations. Bee venom significantly restored hematological profiles by improving RBC count, HGB, and HCT levels while reducing the elevated WBC count, MCV, and MCH values. CRP levels were significantly reduced, reflecting the anti-inflammatory effects of the venom. Also, macroscopic evaluations demonstrated the preservation of colon morphology, while histopathological assessments revealed an improved epithelial integrity with fewer signs of necrosis and cellular atypia. These findings suggest that Apis mellifera intermissa venom holds potential as an adjunct therapeutic agent for suppressing CAC progression, warranting further investigation into its underlying mechanisms and clinical applicability.