Evaluation of antioxidant and antihyperglycemic effects Dovyalis Abyssinica (A.Rich).

Background: The leaves of Dovyalis Abyssinica have been used traditionally for the management of diabetes mellitus. Thus, this study aimed to evaluate the Antioxidant and Antihyperglycemic Effects of Dovyalis Abyssinica leaves crude extract in streptozotocin-induced diabetic mice. Methods: To Evaluate the Antihyperglycemic, and Antioxidant Effects of Dovyalis Abyssinica Leaves Extract in Streptozotocin-Induced Diabetic Mice. Male Swiss albino mice were induced into diabetes using 100 mg/kg of streptozotocin. Mice were allocated randomly into six groups, six mice per group. The body weight and FBG measurements were done on days 0, 7th, 14th and 21st of treatment. Additionally, in vitro Antioxidant Activity of the Extract was determined using a DPPH assay. The data were entered into Epi-Data version 4.6, exported to SPSS version 26.0, and analysed by using a one-way ANOVA followed by a Tukey post hoc test, and P < 0.05 was considered statistically significant. Results: Dovyalis Abyssinica leaves crude extract showed significant (P < 0.05-P< 0.001) blood-glucose-lowering activity. Moreover, the crude extract of D. abyssinica reduced the fasting blood glucose level by 45.13 %, 52.51 %, 54.85 %, and 56.38 %, respectively, for DA 100, DA 200, DA 400, and GLC 5 mg/kg on the 21st day of treatment. After diabetic mice were treated with Dovyalis Abyssinica (100, 200, and 400 mg/kg) for 21 days, there was a significant increase in body weight as compared to diabetic control. Antioxidant activities of the leaf extract was found to be comparable to ascorbic acid with an IC50 of 140.04 µg/ml. Conclusion: The present findings revealed that D. abyssinica leaves could be useful for the management of diabetes mellitus and other abnormalities related to this metabolic disorder. Thus, the present study may support the traditional use of D. abyssinica for diabetes mellitus treatment.

Bacterial etiologies, antimicrobial susceptibility pattern and associated factors among patients suspected sterile body site infections at Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia.

Background: Sterile body locations are usually associated with clinical urgency and life-threatening illnesses, and they are typically contaminated with diverse bacterial etiologies. If the bacteria acquire resistance to antimicrobial drugs, the public health crisis will only worsen. In developing countries, drug-resistant bacteria are common because of poor surveillance, diagnostic capacity, and control measures. Early diagnosis, and assessing the drug resistance and factors associated with infection are important to combat the drug resistance and treatment. This study aimed to assess the bacterial etiologies, antimicrobial susceptibility pattern, and possible associated factors among patients suspected of sterile body sites. Methods: A hospital-based cross-sectional study was conducted from June 2022 to August 2022 at Debre Markos Comprehensive Specialized Hospital in Amhara regional state, Ethiopia. One hundred seven study participants were selected using consecutive convenient sampling techniques. A structured questionnaire was used to collect socio-demographic and clinical data. Gram stain was done for a preliminary report and inoculated into blood agar, MacConkey agar, and chocolate agar and incubated aerobically and micro aerobically at 37°C for 24 h. Antimicrobial susceptibility testing was done by the modified Kirby Bauer's disk diffusion method. Data were analyzed using bivariate and multivariate logistic regression was used. A p-value less than 0.05 is considered as statistically significant. Results: The overall magnitude of sterile body site infection among study participants was 7.5% (14/187). The majority of the isolates were Gram-negative bacteria with the predominant species Enterobacter cloacae accounting for 28.57% (4/14). Among isolates 78.57%(11/14) of them were multidrug-resistant isolates. Being inpatient, co-morbidity, and alcohol consumption were significantly associated with sterile body site infection. Conclusion: In our study, Gram-negative bacteria were the predominant bacteria that infects sterile body fluid. The prevalence of multi-drug resistance bacteria isolates was significantly high. Therefore, before prescribing an empirical treatment, a medical professional should identify the bacterial etiology of sterile body fluids and the susceptibility of microbes to the drug.

Gut microbes as medical signature for the effectiveness of immunotherapy in patients with advanced non-small cell lung cancer.

Lung cancer (LC) is the most common cause of cancer-related death worldwide and poses a severe threat to public health. Immunotherapy with checkpoint blockers has improved the outlook for advanced non-small cell lung cancer (NSCLC) therapy. For the treatment of patients with advanced NSCLC, antibodies such as anti-programmed death 1 (anti-PD1), anti-programmed death ligand 1 (anti-PD-L1), and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) are of paramount importance. Anti-PD-1 and anti-PD-L1 monoclonal antibody therapies are used to block the PD-1/PD-L1 pathway and identify cancerous cells to the body's defenses. Antibodies directed against CTLA-4 (anti-CTLA-4) have also been shown to improve survival rates in patients with NSCLC. Currently, other immunotherapy approaches like neoadjuvant immune checkpoint inhibitors (NAICIs) and chimeric antigen receptor T-cell (CAR-T) therapies are applied in NSCLC patients. NAICIs are used for resectable and early stage NSCLC and CAR-T is used to find more useful epitope sites for lung tumors and destroy cancer cells. A patient's gut microbiota might influence how their immune system reacts to NSCLC immunotherapy. The majority of intestinal microbes stimulate helper/cytotoxic T cells, induce natural killer (NK) cells, activate various toll-like receptors (TLR), build up cluster of differentiation 8 (CD8), increase PD-1 production, and attract chemokine receptors towards cancer cells. Thus, they serve as immune inducers in NSCLC immunotherapy. Nonetheless, certain bacteria can function as immune suppressors by inhibiting DC proliferation, stopping CD28 trafficking, restoring CD80/CD86, increasing immunological tolerance, and upsetting Th17 cells. Therefore, they are prevalent in non-responders with NSCLC immunotherapy.

Histomolecular characterisation of hepatitis B virus induced liver cancer.

Hepatitis B virus (HBV)-associated liver cancer is the third most prevalent cancer-related cause of death worldwide. Different studies have been done on the histomolecular analysis of HBV induced-liver cancer including epigenetics which are dynamic molecular mechanisms to control gene expression without altering the host deoxyribonucleic acid, genomics characterise the integration of the viral genome with host genome, proteomics characterise how gene modifies and results overexpression of proteins, glycoproteomics discover different glyco-biomarker candidates and show glycosylation in malignant hepatocytes, metabolomics characterise how HBV impairs a variety of metabolic functions during hepatocyte immortalisation, exosomes characterise immortalised liver cells in terms of their differentiation and proliferation, and autophagy plays a role in the development of hepatocarcinogenesis linked to HBV infection.

Therapeutic strategies and promising vaccine for hepatitis C virus infection.

Hepatitis C virus (HCV) infection is still a significant global health problem despite therapeutic advancements. Ribavirin and interferon therapy have been the sole available treatments for HCV infection for a number of years with low efficacy. Thus, currently, a number of therapeutic strategies are being used, including nanoparticles (NPs), micro-RNAs such as small interfering RNA (siRNA), RNAi-based gene silencing and antisense oligonucleotide-based microRNA-122, microRNA-155, and short hairpin RNAs (shRNAs), and immunotherapeutic approaches such as anti-programmed cell death 1(PD-1), monoclonal antibodies (mAb or moAb), and monocyte-derived dendritic cells (Mo-DCs). Furthermore, direct-acting antivirals (DAAs) and host-targeting agents (HTA) were also the current therapeutic approaches with great efficacy. In spite of different clinical trials on HCV vaccine developments, nowadays there is no effective HCV vaccine in opposition to virus due to various challenges including genetic diversity, lack of immunocompetent small animal models, shortage of HCV vaccination testing alternatives, lack of an effective tissue culture method for replicating HCV, and inadequate knowledge regarding to immune responses against HCV infection. Nowadays, mRNA vaccine, recombinant viral vector, peptides vaccine, virus-like particles, DNA vaccine, rational designed vaccine, and recombinant polyantigenic T-cell-based vaccine are novel promising candidates for HCV vaccine based on various clinical trials. This review summarizes the different therapeutic approaches and the advancements of vaccine candidates for HCV infection.

Reduced protective efficacy of hepatitis B vaccine among fully vaccinated children in Ethiopia.

BACKGROUND: Hepatitis B vaccination is recommended for all children at birth within 24 hours or during childhood. OBJECTIVE: This study was aimed to evaluate protective efficacy of hepatitis B vaccine and estimate the sero-prevalence of hepatitis B virus infection among vaccinated children. MATERIALS AND METHODS: A community-based cross-sectional study was conducted from March, 2021 to October, 2021 in Debre Markos town. A simple random sampling technique was used to select 165 fully vaccinated children aged 5-12 years old. A serum sample was used to determine hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody titer (anti-HBs) using ELISA. RESULTS: The seroprevalence of HBsAg and anti-HBc anti-body was found to be 4.2% and 4.8% respectively. Of 165 fully vaccinated children, 129 (78.2%) had anti-HBs titer ≥ 10 mIU/ml. Among 129 sero-protected children, 76 (58.9%) were hypo-responders whereas the rest 53 (41.1%) were good responders. Those children within the age group of 5-7 years were 2.9 times (AOR: 2.873, 95% CI: 1.156, 7.141) (P<0.023) more likely to respond to HBV vaccine. Multivariate logistic regression revealed that children who were born from HBV positive mothers (AOR 3.917, 95% CI: 1.456, 5.365, P<0.027) and those who had history of injectable medications (AOR 9.232, 95% CI: 1.503, 11.697, P<0.016) were more likely to be HBsAg positive. Children who had history of hospital admission (AOR 6.973, 95% CI: 1.495, 8.530, P<0.013) were more likely to be anti-HBcAb positive. CONCLUSIONS: There was an intermediate prevalence of childhood HBV infection despite being vaccinated suggesting low protective efficacy of hepatitis B vaccine in the study area.

Prevalence and Predictors of Pulmonary Tuberculosis among Prison Inmates in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Introduction: Prisoners in Sub-Saharan Africa (SSA) are at a high risk of tuberculosis (TB) infection due to overcrowding and poor ventilation. Consequently, TB is a leading cause of morbidity and mortality in prison, and many inmates face a number of barriers to TB control and had limited information in the region. Thus, the aim of this systematic review and meta-analysis was to estimate the overall pooled prevalence of pulmonary TB and predictors among prison inmates in SSA. Methods: From 2006 to 2019, a systematic review and meta-analysis was conducted using various databases, including PubMed, Embase, Web of Science, and Scopus. The data were extracted in Microsoft Excel using a standardized data extraction format, and the analysis was carried out with STATA version 14. To detect heterogeneity across studies, the I2 and the Cochrane Q test statistics were computed. To determine the overall prevalence of TB and predictors among prison populations, a random effect meta-analysis model was used. Results: Of the 3,479 retrieved articles, 37studies comprising 72,844 inmates met the inclusion criteria. The pooled prevalence of pulmonary TB among prison inmates in SSA was 7.74% (95% CI: 6.46-8.47). In the subgroup analysis, the highest prevalence was found in the Democratic Republic Congo (DRC) (19.72%) followed by Zambia (11.68%) and then Ethiopia (9.22%). TB/HIV coinfection (OR 4.99 (95% CI: 2.60-9.58)), Body mass index (BMI < 18.5) (OR 3.62 (95% CI: 2.65-6.49)), incarceration (OR 4.52 (95% CI: 2.31-5.68)), and previous TB exposure (OR 2.43 (95% CI: 1.61-3.56)) had higher odds of pulmonary TB among inmates. Conclusion: The prevalence of pulmonary TB among SSA prison inmates was found to be high as compared to total population. TB/HIV coinfection, BMI, incarceration duration, and TB exposure were all predictors with pulmonary tuberculosis in prison inmates. As a result, emphasizing early screening for prisoners at risk of pulmonary TB is an important point to achieving global TB commitments in resource-limited settings.

Antigen Recognition and Immune Response to Acute and Chronic Hepatitis B Virus Infection.

The antigen recognition and immune response to acute and chronic hepatitis B virus (HBV) infections are the result of both the innate and adaptive immune response. The innate immune response comprises Dendritic Cells (DCs), which served as professional antigen-presenting cells and a bridge between innate and adaptive immunity, Kupffer cells and inflammatory monocytes for the continuous inflammation of hepatocyte, neutrophils for hepatic tissue damage due to acute inflammation, type I interferons (IFN), which induce an antiviral state on infected cells, directs natural killer (NK) cells to kill virally infected cells, reduces the population of infected cells, and promotes the effective maturation and site recruitment of adaptive immunity through the production of pro-inflammatory cytokines and chemokines. Through stimulating B cells, T-helper, and cytotoxic T cells, the adaptive immune system also protects against hepatitis B infection. During HBV infection, a network of cell types that can either play protective or harmful functions creates the anti-viral adaptive immune response. These many elements, such as Cluster of differentiation four (CD4) T cells (traditionally known as helper T cells), are potent cytokine producers and necessary for the effective maturation of effector cytotoxic cluster of differentiation eight (CD8) T cells and B cell antibody production. By cytolytic and non-cytolytic processes, CD8 T cells are able to eliminate HBV-infected hepatocytes and directly detect virus-infected cells, and circulating CD4+ CD25+ regulatory T cells for the modulation of immune system. In order to avoid reinfection, B cells can produce antibodies that destroy free viral particles. Moreover, by presenting HBV antigens to helper T cells, B cells may also influence how well these cells operate.