Negative Group Research Articles

Antidiabetic and Antihyperlipidemic Activity of Ethanolic Extract of Mentha viridis in Alloxan Induced Diabetic Rats

This research was designed to examine the phytochemicals of Mentha viridis (M. viridis) ethanolic extract and the antidiabetic and antihyperlipidemic activities in alloxan-induced animal models. Diabetes was induced chemically by administering a unit dose of alloxan at 120 mg/kg BW. After alloxan induction, hyperglycemic rats were dealt with ethanolic extract of leaf and whole plant, metformin, and a mixture of leaf extract with metformin and whole plant extract with metformin for two weeks. Ethanolic extract of leaf and whole plant, metformin, and a combination of both leaf and whole plant extract with metformin therapies reduced glucose levels in the blood compared with the diabetic negative control group after two weeks of treatment. However, among the therapies, the ethanolic leaf extract and the combination of whole plant extracts with metformin were found to be the most effective (p<0.05), with reductions of 62.82% and 72.89%, respectively. After diabetes induction, the serum level of TG (triglycerides), TC (total cholesterol), LDL-C (low-density lipoprotein-cholesterol) escalated notably (p<0.05), and HDL-C (high-density lipoprotein-cholesterol) level decreased remarkably (p<0.05) in hyperglycemic rats as opposed to healthy normal rats. Ethanolic leaf extract and a combination of whole plant extract with metformin significantly minimized the elevated extent of TG and LDL-C. They surged HDL-C, but the TC level was reduced by whole plant extract only after two weeks of treatment. The standard procedures were used to identify the phytochemical compounds of the medicinal plant M. viridis. The phytochemical compounds such as alkaloids, resins, tannins, phenols, flavonoids, steroids, and terpenoids appeared in the ethanolic leaf extract of M. viridis. The findings suggest that M. viridis might provide better glycemic control and hypolipidemic effect in diabetic rats when administered alone or combined with oral antidiabetic agents. Incorporating M. viridis extract with metformin in improving hyperglycemic and hyperlipidemic conditions in diabetic rats proves that M. viridis has a synergistic effect, which could enhance the antidiabetic activity of oral hypoglycemic agents.

Interleukin-17 Gene Polymorphisms and Hepatitis B Virus Infection in a Sample of Iraqi Patients

Hepatitis B, a chronic inflammatory liver condition, constitutes a significant global health issue, with 3 million new cases and over 1 million deaths annually (when combined with hepatitis C). The infection may be acute or chronic, and it transmits horizontally by contact with biological fluids such saliva, blood, semen, tears, vaginal secretions, or perinatal fluids following childbirth, which are transferred from mother to infant. Infections can be easily prevented with immunization, typically administered shortly after birth; nevertheless, if neglected, chronic hepatitis B may lead to severe outcomes, including liver cancer or cirrhosis. Interleukin-17A, a pro-inflammatory cytokine, is essential in the immune response to many infections and is implicated in autoimmune diseases. The cytokine interleukin-17 (IL-17A) is only secreted by activated T cells. cDNA of IL-17 has been isolated and cloned from murine hybridomas (cytotoxic T lymphocyte antigen 8 (CTLA-8)). Cytokine imbalance is a crucial factor in the progression and growth of the hepatitis B virus (HBV). A cross-sectional study was conducted including 180 patients with HBV infection at the Digestive and Liver Diseases Teaching Hospital in Baghdad province, from December 14, 2022, to February 15, 2023. This study comprised two groups: the first group consisted of 40 HBV antibody-positive patients, while the second group included 40 HBV antibody-negative patients, along with a control group of 20 individuals. A blood sample of 5 ml was collected from each patient, divided into 2 ml in an anticoagulated EDTA tube and 3 ml in a gel tube. Whole blood with anticoagulated samples was utilized under optimal conditions for DNA extraction, while serum was isolated from blood for biochemical tests. The study comprised 180 patients, categorized into three groups: HBV Positive, HBV Cleared, and Control. The HBV Positive cohort consists of 99 individuals, comprising 54 males (54.45%) and 45 females (45.45%). The average age in this cohort is 42.52 years, accompanied by a standard deviation of 15.13 years. Of these individuals, 84 (84.85%) are wed. The HBV Cleared group has 45 individuals, including 24 males (53.34%) and 21 females (46.67%). The average age in this cohort is 48.43 years, with a standard deviation of 13.98 years. A predominant 39 persons (86.67%) are wed. The Control group comprises 36 individuals, primarily male, consisting of 24 men (66.67%) and 12 females (33.34%). Genotype distribution for two genetic markers, rs2275913 and rs10484879, among three groups: HBV Positive, HBV Negative, and Control. In the HBV Positive group for the rs2275913 marker, the AA genotype is present in 30 patients, the AG genotype in 36 patients, and the GG genotype in 36 patients. In the HBV Negative group, the AA genotype is observed in 9 patients, the AG genotype in 12 patients, and the GG genotype in 21 patients. Multiple research investigations have concentrated on the role of SNPs in the IL17A gene, particularly rs2275913 and rs10484879, in the susceptibility to chronic HBV infection. The polymorphisms were specifically examined for their possible impact on immune response and disease progression in patients infected with HBV. A study of the Han Chinese population demonstrated a significant correlation between the GG genotype and G allele of rs2275913 and an increased risk of HBV infection, suggesting a causal relationship with heightened susceptibility to viral infection.

Immunogenicity of Brucella Trivalent Immunogen-Containing Polyethyleneimine Nanostructure Targeted with LPS in a Mouse Model.

Brucella is a facultative intracellular gram-negative coccobacillus. It is nonsporulating and reproduced in macrophage phagosomes. The use of nanostructures as drug and vaccine carriers has recently received attention due to their ability to control the release profile and protect the drug molecules. This study presents a suitable nano-polyethyleneimine formulation to be used as an immunoadjuvant and LPS along with trivalent candidate antigens of TF, BP26, and omp31 to selectively stimulate the immune response. After designing and evaluating the immunogenic structure by databases and bioinformatics software, recombinant protein cloning and gene expression were performed in Escherichia coli BL21 bacteria. This protein was extracted from the cultured cells, purified by Ni-NTA column. After placing the antigen inside the polyethyleneimine nanostructure, various properties of the nanoparticles, including their size, zeta potential, and retention rate for injection and inhalation of mice, diffusion efficacy, and antigen binding evaluation were evaluated. Mice were treated with different groups of antigens and nanoparticles on days 0, 10, 24, and 38. Two weeks after the last injection, the level of cytokines were investigated in spleen cells, including IFN-γ, IL-4, and IL-12. The serum concentration of IgG2a and IgG1 antibodies were also assessed. The response was consistent with significant production of IgG1, IgG2a, IFN-γ21, IL-12, and IL-4 compared to the controls (P < 0.05). Compared to the positive and negative control groups, recombinant protein and nanoparticles showed a good response in subsequent injections with live bacterial strains. The present study also revealed the potential of the developed recombinant protein as a candidate in the design and manufacture of subunit vaccines against Brucella species. This protein stimulates cellular and humoral immune responses compared to the positive control groups. These findings can be useful in the prevention and control of brucellosis and pave the way for further research by researchers around the world.

Enhanced clindamycin delivery using chitosan-coated niosomes to prevent Toxoplasma gondii strain VEG in pregnant mice: an experimental study

BackgroundCongenital toxoplasmosis occurs when a pregnant woman becomes infected with Toxoplasma gondii (T. gondii) for the first time. Treatment typically involves antimicrobial medications, with spiramycin commonly used to prevent transmission. However, spiramycin's effectiveness is limited due to poor placental penetration. Clindamycin, another antibiotic, can cross the placenta but reaches the fetus at only half the maternal concentration. Encapsulating the drug in chitosan-coated niosomes (Cs-Nio) could enhance its effectiveness by targeting specific organs and ensuring sustained release. To address the challenges of using clindamycin, a niosome-coated chitosan system was investigated for treating congenital toxoplasmosis caused by the VEG strain of T. gondii in an animal model.MethodsPregnant mice were infected with VEG strain of T. gondii on the 12th day of pregnancy, followed by treatment with various drugs across six groups. The treatments included chitosan-coated niosomes loaded clindamycin (Cs-Nio-Cli) and other controls. Parasitological evaluations (microscopic examination and real-time PCR), along with histopathological and immunological assessments were conducted to assess treatment efficacy. Finally, statistical analysis was conducted using GraphPad Prism 8.0 and SPSS 26, comparing test and control groups with T test and Mann–Whitney test. A p ≤ 0.05 was considered statistically significant.ResultsThe study found that treatment with Cs-Nio-Cli significantly reduced the number of T. gondii cysts in the brain and eyes (97.59% and 92.68%, respectively) compared to the negative control group. It also mitigated inflammatory changes, prevented cell death, and reduced vascular cuffs in the brain. In addition, Cs-Nio-Cli treatment decreased bleeding, placental thrombosis, and inflammatory cell infiltration in the placenta while improving eye tissue health by reducing retinal folds and bleeds. Immunologically, nanoclindamycin treatment resulted in lower TNF-α cytokine levels and higher IL-10 levels, indicating an enhanced anti-inflammatory response.ConclusionsAlthough Cs-Nio-Cli demonstrates promise in reducing the transmission of congenital toxoplasmosis and mitigating the effects of congenital toxoplasmosis, additional research is necessary to determine the optimal treatment regimens for the complete eradication of the parasite in the fetus.

Ameliorating effects of natural herbal supplements against water-borne induced toxicity of heavy metals on Nile tilapia, (Oreochromis niloticus)

The efficacy of herbal supplements in mitigating heavy metals (HMs) toxicity was investigated using a widely grown fish, the Nile tilapia (Oreochromis niloticus). The experiment was conducted over two phases: during the stress phase, the experimental fishes were exposed to sub-lethal concentrations of HMs, including lead, cadmium, zinc, and copper for 15 days; following which during the feeding phase, herbal supplements were given for 70 days to ameliorate their effects. Seven groups were established: the control negative group (CON−ve), control positive group (CON+ve, without any treatment), and five groups with supplementation of 1% turmeric (TUR), cinnamon (CIN), ginger (GIN), garlic (GAR), and their mixture (MIX), respectively. A total of 315 fishes were distributed evenly in experimental tanks (15 fishes per tank, in triplicates). The results revealed that exposure to HMs led to significant (p < 0.05) alterations in all the tested parameters, i.e., liver damage and growth reduction. The herbal supplements, especially the MIX groups, ameliorated the harmful effects of HMs and restored fish growth, digestibility, carcass composition, and liver health. In conclusion, the study demonstrated that the herbal supplements were effective in reducing the HMs-linked toxicity in Nile tilapia. Future studies pertaining to the mechanisms facilitated by the various herbal bioactive substances-linked tolerance to HMs in fishes are warranted.

Evaluation of the protective dose-dependent effect of metformin for induced osteoarthritis in rats.

To evaluate the potential protective effect of metformin against osteoarthritis development in rats. The experimental study was conducted at the Iraqi Centre for Cancer Research and Medical Genetics, Mustansiriyah University, Baghdad, Iraq, from December 2021 to February 2022, and comprised male Sprague- Dawley mice who were divided into 5 equal groups: negative control group, osteoarthritis group subjected to monoiodoacetate induction, positive control group treated with celecoxib 30mg/kg, metformin 100mg/kg group, and metformin 200mg/kg group. Body mass index, inflammatory biomarkers, and serum C-terminal cross-linked telopeptide of type II collagen levels were noted for all the animals. Data was analysed using SPSS 24. Of the 35 mice, 7(20%) were in each of the 5 groups. Compared to the osteoarthritis group, metformintreated mice showed significantly reduced body mass index, inflammatory biomarker levels, and blood levels of Cterminal cross-linked telopeptide of type II collagen (p=0.05). Metformin 200mg/kg treatment had more beneficial effects than 100mg/kg dose on inflammatory biomarkers and serum C-terminal cross-linked telopeptide of type II collagen (p=0.05). A beneficial protective effect against the onset of osteoarthritis was produced by metformin in a dosedependent way. Additionally, metformin could lessen cartilage damage as demonstrated by a decrease in the serum levels of C-terminal cross-linked telopeptide of type II collagen in the osteoarthritis group.

Post-COVID-19 condition in children: epidemiological evidence stratified by acute disease severity.

To determine the prevalence of pediatric Post-COVID-19 condition (PPCC), identify risk factors, and assess the quality of life in children with differing severities of acute COVID-19. During a prospective longitudinal study with a 1-year follow-up, we compared non-hospitalized (mild) and hospitalized (severe) COVID-19 cases to a negatively tested control group. 579 children were included in this study. Of these, 260 had mild acute disease (median age:8, IQR:6-10), 60 had severe acute disease (median age:1, IQR:0.1-4.0), and 259 tested negative for SARS-CoV-2 (NT) (median age:8, IQR:5-10). At three months, 14.6% of the SARS-CoV-2 positive mild group (RR:6.31 (CI 95%: 2.71-14.67)) and 29.2% of the severe group (RR:12.95 (CI 95%: 5.37-31.23)) reported sequelae, versus 2.3% of the NT group. PPCC prevalence in the mild group decreased from 16.1% at one month to 4.4% at one year. Children with PPCC exhibited lower physical health-related quality of life scores and higher fatigue scores than the NT children. Severe acute COVID-19 in children leads to a higher PPCC prevalence than in mild cases. PPCC prevalence decreases over time. Risk factors at three months include prior medical history, hospital admission, and persistent fatigue one month after a positive test. We demonstrate children with severe COVID-19 are more likely to develop Post-COVID-19 condition than those with mild or no infections, and highlights the risk factors. Here we have stratified by acute disease severity, prospectively included a negative control group, and have demonstrated the heterogeneity in prevalence when utilizing various recent definitions of post-COVID. Identifying risk factors for pediatric post-COVID and highlighting the heterogeneity in prevalence based on various current definitions for post-COVID should aid in correctly identifying potential pediatric post-COVID cases, aiding in early intervention.

Status quo and factors influencing dyadic disease appraisal in chronic heart failure based on latent profile analysis in Northern Sichuan Province, China

PurposeThis study explored potential categories of dyadic disease appraisal differences among patients hospitalized with chronic heart failure (CHF) in China and analyzed the main factors influencing these categories.MethodsA survey was conducted using various tools and scales, including the Chinese version of the Memorial Heart Failure Symptom Appraisal Scale, Heart failure self-care index scale, Social Support Rating Scale, Zarit burden interview, and Self-rating anxiety scale. The data was collected from patients who were hospitalized with CHF in the cardiology department of one of two tertiary hospitals in Nanchong City, China. The dyadic disease appraisal categories were identified using latent profile analysis (LPA). Multiple logistic regression analysis was also employed to analyze the factors influencing the formation of potential categories of differences in dyadic disease appraisal in CHF patients.ResultsA total of 262 pairs of hospitalized CHF patients and their caregivers participated in this study. The dyadic disease appraisal of CHF patients was potentially categorized as the "negative difference group" (28 individuals, 10.7%) and the "positive or convergence group" (234 persons, 89.3%). The results showed that the factors influencing the categorization of dyadic disease appraisal differences included the patient's social support, disease progression, and Caregivers anxiety level, burden, gender, educational attainment, and age (p < 0.05).ConclusionThe study findings demonstrated heterogeneity between the two groups of CHF patients in the dyadic disease appraisal. Therefore, it is necessary to focus on patients who have a brief duration of illness and limited social support. Specifically, it is important to prioritize support for female caregivers who are 65 years or older, have lower levels of educational attainment, and experience a significant burden and anxiety. Regular implementation of support person-bilateral co-management strategies can effectively reduce differences in how the disease is perceived and enhance the overall well-being of both caregivers and patients.

Homologous Targeting Effect of Cancer Cell-Derived Liposomes (Memposomes) Mediated by Cell Adhesion Molecules: Role of E-cadherin.

Cell membrane-derived liposomes, termed Memposomes, serve as promising carriers for drug delivery due to their ability to closely mimic cells and efficiently target specific cells. Liposomes derived from cancer cell membranes, in particular, exhibit homologous targeting capabilities, making them potential candidates for cancer-specific drug delivery. However, the underlying mechanisms and specific proteins responsible for this homologous targeting phenomenon remain debated. This study focuses on the role of E-cadherin, a cell adhesion molecule implicated in homophilic adhesion, in influencing the homologous targeting ability of Memposomes derived from cancer cell membranes. E-cadherin expression patterns were assessed in various cell lines, categorizing them into E-cadherin-positive and -negative groups. Memposomes were produced for each group, and their targeting tendencies were evaluated. This study confirmed that E-cadherin expression significantly influenced the homologous targeting ability of the Memposomes. The cell lines with higher E-cadherin expression levels exhibited a more pronounced homologous targeting effect. This research demonstrates that cell adhesion molecules, particularly E-cadherin involved in homophilic adhesion, play a pivotal role in influencing the cell targeting ability of Memposomes. This study further validates the stability, safety, and purity of Memposomes, emphasizing their potential as effective drug delivery vehicles for the development of cell-specific therapies.

PTEN Deficiency Induced by Extracellular Vesicle miRNAs from Clonorchis sinensis Potentiates Cholangiocarcinoma Development by Inhibiting Ferroptosis.

The human phosphatase and tensin homolog (PTEN) is a tumor suppressor. A slight deficiency in PTEN might cause cancer susceptibility and progression. Infection by the liver fluke Clonorchis sinensis could lead to persistent loss of PTEN in cholangiocarcinoma. However, the mechanism of PTEN loss and its malignant effect on cholangiocarcinoma have not yet been elucidated. Extracellular vesicles secreted by Clonorchis sinensis (CS-EVs) are rich in microRNAs (miRNAs) and can mediate communication between hosts and parasites. Herein, we delved into the miRNAs present in CS-EVs, specifically those that potentially target PTEN and modulate the progression of cholangiocarcinoma via ferroptosis mechanisms. CS-EVs were extracted by differential ultra-centrifugation for high-throughput sequencing of miRNA. Lentiviral vectors were used to construct stably transfected cell lines. Erastin was used to construct ferroptosis induction models. Finally, 36 miRNAs were identified from CS-EVs. Among them, csi-miR-96-5p inhibited PTEN expression according to the predictions and dual luciferase assay. The CCK-8 assay, xenograft tumor assays and transwell assay showed that csi-miR-96-5p overexpression and PTEN knockout significantly increased the proliferation and migration of cholangiocarcinoma cells and co-transfection of PTEN significantly reversed the effect. In the presence of erastin, the cell proliferation and migration ability of the negative transfection control group were significantly impaired, although they did not significantly change with transfection of csi-miR-96-5p and PTEN knockout, indicating that they obtained ferroptosis resistance. Mechanistically, csi-miR-96-5p and PTEN knockout significantly inhibited ferroptosis through a decrease in ferrous ion (Fe2+) and malondialdehyde (MDA), and an increase in glutathione reductase (GSH), Solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In conclusion, loss of PTEN promoted the progression of cholangiocarcinoma via the ferroptosis pathway and csi-miR-96-5p delivered by CS-EVs may mediate this process.

The dose of remimazolam combined with sufentanil for the induction of general anesthesia in obese patients undergoing bariatric surgery: an up-and-down sequential allocation trial.

Background and purpose: Remimazolam is a newly developed benzodiazepine drug with water-soluble, esterase degradation, and ultra-short-acting properties. The dose for general anesthesia induction in obese patients was not known. This study aimed to determine the optimal dose of remimazolam in combination with sufentanil for the induction of general anesthesia in obese patients. Methods: It was a prospective observational study. We recruited 46 patients scheduled for bariatric surgery from October 2022 to December 2023. One patient refused to provide informed consent, and six patients were receiving psychotropic medication. Thirty-nine patients were enrolled. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale was used to assess the patient's response. The dose of sufentanil was 0.5 µg/kg (lean body weight [LBW]). The initial dose of remimazolam was 0.3mg/kg (LBW). The dose of remimazolam was modified using the up-and-down allocation technique. Successful sedation (negative group) was characterized by achieving a MOAA/S score ≤ 1 within 3min of commencing remimazolam infusion. If negative, the next patient received a low-level dose at a ratio of 0.9. Failed sedation (positive group) was defined as a MOAA/S score of >1 within 3min of commencing remimazolam infusion. The patients in the positive group received propofol 0.5mg/kg as a remedial measure, and the next dose was increased to a higher level. The primary outcome was to determine the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam in combination with sufentanil 0.5 µg/kg for induction in obese patients. The secondary outcome was to determine the occurrence of adverse effects such as hypotension, hypertension, and intraoperative awareness. Results: The ED50 and ED95 values of remimazolam (LBW) combined with sufentanil (0.5 µg/kg) (LBW) were 0.115mg/kg (95% CI: 0.072-0.137) and 0.179mg/kg (95% CI: 0.150-0.434), respectively, and the time of loss of consciousness in the negative group was 120.13 ± 25.03s. The cardiovascular system was stable during the induction period. The incidence of post operative nausea and vomiting (PONV) was 38.5% in 39 patients. Respiratory depression, allergic reaction, intraoperative awareness, and delayed emergence were not observed in any patient. Conclusion: Remimazolam combined with sufentanil (0.5 µg/kg) (LBW) can be effectively used for general anesthesia induction in obese patients. The ED50 and ED95 values of remimazolam (LBW) were 0.115mg/kg and 0.179mg/kg, respectively. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200065602.

Effect of Aloe vera Gel and Sodium Metabisulphite on Expression of Fibroblast Growth Factor in Incision Wound of Rats

An incision wound is a wound caused by being sliced. Two ingredients that play a key role in the wound-healing process are glucomannan and acemannan, which are rich in polysaccharides and growth hormones. Growth hormones stimulate fibroblast activity and proliferation. The present study involved 35 Sprague Dawley male rats, aged 2-3 months old and weighing 200-300 grams. The study comprised seven groups including, negative control group (G1), positive control (aquades, G2), betadine 10% (G3), gel base (0.5 mg, G4), gel base + sodium metabisulfite 0.2 gr (G5), gel base + Aloe vera 5% (G6), and gel base + Aloe vera 5% + sodium metabisulfite 0.2 gr (G7). Each group had five replications. Initially, a 4-cm incision was made on the dorsal skin of each rat. The study lasted 15 days with observations made on days 3, 7, and 15. After the observation period, the rats were anesthetized and then terminated to collect skin tissues for microscopic examination. The tissue samples were then stained immunohistochemically to assess fibroblast growth factor (FGF) expressions. The results showed that the highest FGF expression was observed in the 5% Aloe vera + 2% metabisulfite group (G7), while the lowest FGF expression was in the negative control group (G1). It is concluded that Aloe vera L. extract gel at 5% + 2% metabisulfite (G7) significantly enhances the expression of FGF. Keywords: Aloe vera L, Fibroblast growth factor, Incision wound, Skin, Sodium metabisulfite

An in vitro evaluation of intravenous lipid emulsion on three common canine toxicants.

To determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time. Seven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group). Injectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, Intralipid® ) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 g for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at -80°C prior to analysis. A significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration. ILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment in vitro study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis.

Test of the Effectiveness of Earthworm Flour (Lumbricus rubellus) Gastroretentive Mucoadhesive Granule Formulation on Male White Rats (Rattus norvegicus) Infected with Salmonella typhi

Lumbricus rubellus contains lumbricin which is efficacious for treating typhoid fever. The aim of the research was to determine the effectiveness of gastroretentive mucoadhesive granule preparations from earthworm flour. This study used 30 male Wistar rats which were divided into 6 groups which were given orally, the normal and negative control groups were given Na-CMC, the positive control group was given chloramphenicol, and the treatment group was given doses of 200 mg/kgBW, 400 mg/kgBW and 800 mg/kgBW. mg/kgBB gastroretentive mucoadhesive granules earthworm flour. The results of body temperature measurements, on day 7 the control group obtained results of ±37.08, ±39.00 and ±38.09 respectively, and the treatment group obtained results of ±38.09, ±38.09 and ±38.07 respectively. On day 21, the control group obtained results of ±37.08, ±39.00 and ±38.09, respectively, and the treatment group obtained results of ±38.09, ±38.09 and ±38.07, respectively. The Widal test results on the 7th day were positive and after 14 days of administering the preparation on the 21st day the results were negative. It was concluded that the effective dose for typhoid fever therapy was a dose of 400 mg/kgBW.

Effect of hydroalcoholic extract of Sambucus nigra on superficial digital flexor tendon repair in rabbit by ultrasonography and histopathology.

Adult tendon tissue has limited and slow regenerative capacity. Sambucus nigra plant possesses antioxidant and anti-inflammatory attributes. This study aimed to evaluate the effect of hydroalcoholic extract of this plant's fruit on superficial digital flexor tendon repair in rabbits (SDFT). Twenty-five male New Zealand white rabbits weighing 1.5-2kg were selected, quarantined and randomly divided into four groups of six. By performing a partial left posterior limb tenotomy, differentiating the SDFT and creating multiple scrapes were performed. During 3 consecutive days post-surgery, the positive control group was injected with 0.5mg/kg dexamethasone, whereas the treatment groups received extract doses of 200 and 400mg/kg, respectively. The negative control group did not receive any medication. Evaluation of sonographic and histopathological parameters was conducted on days 0, 7 and 28 post-surgeries. Findings were analysed and compared using SPSS22. Both treatment groups showed significant differences in echogenicity, and collagen fibre alignment compared to the control and positive control groups, in sonographic evaluation. Histopathological examination revealed fewer inflammatory cells and increased collagen fibre formation in the treatment groups compared to the other two groups. No significant difference in angiogenesis was observed among the groups on days 7 and 28 (p value <0.05). The results indicate that the S. nigra fruit extract, by stimulating collagen synthesis and reducing inflammation, effectively accelerates the healing process of injured tendons.

Recurrent stroke admissions with vs without COVID-19 and associated in-hospital mortality: A United States nationwide analysis, 2020.

Coronavirus disease 2019 (COVID-19) has been shown to increase the risk of stroke. However, the prevalence and risk of recurrent stroke in COVID-19 patients with prior stroke/transient ischemic attack (TIA), as well as its impact on mortality, are not established. To evaluate the impact of COVID-19 on in-hospital mortality, length of stay, and healthcare costs in patients with recurrent strokes. We identified admissions of recurrent stroke (current acute ischemic stroke admissions with at least one prior TIA or stroke) in patients with and without COVID-19 using ICD-10-CM codes using the National Inpatient Sample (2020). We analyzed the impact of COVID-19 on mortality following recurrent stroke admissions by subgroups. Of 97455 admissions with recurrent stroke, 2140 (2.2%) belonged to the COVID-19-positive group. The COVID-19-positive group had a higher prevalence of diabetes and chronic kidney disease vs the COVID-19 negative group (P < 0.001). Among the subgroups, patients aged > 65 years, patients aged 45-64 years, Asians, Hispanics, whites, and blacks in the COVID-19 positive group had higher rates of all-cause mortality than the COVID-19 negative group (P < 0.01). Higher odds of in-hospital mortality were seen in the group aged 45-64 (OR: 8.40, 95%CI: 4.18-16.91) vs the group aged > 65 (OR: 7.04, 95%CI: 5.24-9.44), males (OR: 7.82, 95%CI: 5.38-11.35) compared to females (OR: 6.15, 95%CI: 4.12-9.18), and in Hispanics (OR: 15.47, 95%CI: 7.61-31.44) and Asians/Pacific Islanders (OR: 14.93, 95%CI: 7.22-30.87) compared to blacks (OR: 5.73, 95%CI: 3.08-10.68), and whites (OR: 5.54, 95%CI: 3.79-8.09). The study highlights the increased risk of all-cause in-hospital mortality in recurrent stroke patients with COVID-19, with a more pronounced increase in middle-aged patients, males, Hispanics, or Asians.

Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction. We recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in Aβ negative (-) and Aβ positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs. We identified SNPs related to cortical thickness using SCCA in Aβ negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating Aβ uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of CHRNA2, NECTIN2, and HLA genes. Our findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.

LncRNA Pvt1 aggravates cardiomyocyte apoptosis via the microRNA-216/Ccnd3 axis

ObjectiveOur study aims to evaluate the role of long non-coding RNA variant translocation gene Pvt1 in cardiomyocyte apoptosis, as well as the potential targets and mechanisms involved in Pvt1-miRNA-mRNA axis. Methods1.Pvt1 knockdown in cells by transfection with small interfering RNA (si-Pvt1), HL-1 cells were randomly divided into control group, hypoxia group, hypoxia + negative control group and hypoxia + si-Pvt1 group. Apoptosis-related genes expression was detected by Western blot assay, RT-qPCR and Flow cytometry assay. 2.Pvt1 knockdown model (sh-Pvt1) was established by injecting adeno-associated virus (AAV) vector shRNA-Pvt1 into the caudal vein 7 days before myocardial infarction, and echocardiography was used to measure cardiac function 7 days after myocardial infarction induced by ligation of the left anterior descending branch. HE staining was used to evaluate the pathological injury of mouse heart tissue, and the apoptotic protein expression was detected by Western blot. 3.lncRNA-related microRNAs were predicted by bioinformatics tools and further verified by dual luciferase experiment. Western blot analysis was used to identify the expression of apoptotic genes following the simultaneous transfection of si-Pvt1 and miR-216 mimics. Genes differentially expressed in hypoxia + si-NC and hypoxia + si-Pvt1 groups were identified by RNA sequencing. These genes were then compared with the target genes of miR-216 predicted by bioinformatics tools. The gene of interest Ccnd3 was excluded from the analysis. Western blot analysis was used to assess the expression of Apoptosis-related proteins in HL-1 cells co-transfected with miR-216 mimics and overexpressed Ccnd3. Results1. Pvt1 was highly expressed in HL-1 induced by hypoxia, and Pvt1 knockdown can reduce cell apoptosis in hypoxia cells. 2. MI causes myocardial injury in mice, and inhibition of Pvt 11 can improve the cardiac function of mice with myocardial infarction, prevent some inflammatory cell infiltration, and reduce myocardial cell apoptosis. 3. Pvt1 acts as a sponge for miR-216 and promotes the expression of Ccnd3. ConclusionPvt1 may promote myocardial infarct-induced apoptosis through the miR-216/Ccnd3 axis.

Positive impact of indicaxanthin from Opuntia ficus-indica fruit on high-fat diet-induced neuronal damage and gut microbiota dysbiosis.

Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet; the high-fat diet group was fed a high-fat diet; and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally (0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet-induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids (Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles (Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet-induced neuronal damage and on the gut microbiota composition in obese mice.

Interrater agreement and variability in visual reading of [18F] flutemetamol PET images.

The purpose of this study was to validate the concordance of visual ratings of [18F] flutemetamol amyloid positron emission tomography (PET) images and to investigate the correlation between the agreement of each rater and the Centiloid (CL) scale. A total of 192 participants, clinically classified as cognitively normal (CN) (n = 59), mild cognitive impairment (MCI) (n = 65), Alzheimer's disease (AD) (n = 55), or non-AD dementia (n = 13), participated in this study. Three experts conducted visual ratings of the amyloid PET images for all 192 patients, assigning a confidence level to each rating on a three-point scale (certain, probable, or neither). The positive or negative determination of amyloid PET results was made by majority vote. The CL value was calculated using the CapAIBL pipeline. Overall, 101 images were determined to be positive, and 91 images were negative. Of the 101 positive images, the three raters were in complete agreement for 92 images and in disagreement for 9 images. Of the 91 negative images, the three raters were in complete agreement for 75 images and in disagreement for 16 images. Interrater reliability among the three experts was particularly high, with both Fleiss' kappa and Conger's kappa measuring 0.83 (0.76-0.89). The CL values of the unanimous positive group were significantly greater than those of the other groups, whereas the CL values of the unanimous negative group were significantly lower than those of the other groups. Images with rater disagreement had intermediate CLs. In cases with a high confidence level, the positive or negative visual ratings were in almost complete agreement. However, as confidence levels decreased, experts' visual ratings became more variable. The lower the confidence level was, the greater the number of cases with disagreement in the visual ratings. Three experts independently rated 192 amyloid PET images, achieving a high level of interrater agreement. However, in patients with intermediate amyloid accumulation, visual ratings varied. Therefore, determining positive and negative decisions in these patients should be performed with caution.