Significant Decrease In Levels Research Articles

Molecular mechanism analysis of a family with hereditary coagulation F Ⅺ deficiency caused by compound heterozygous mutations

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.

Investigation of DNA damage and inflammatory marker profile in patients after bariatric surgery

Abstract
 Purpose: Obesity is a significant risk factor in the development of many serious diseases. The most prominent ones among them are diabetes and coronary heart disease. Elevated blood sugar levels in obese individuals lead to increased susceptibility to infections due to the suppression of the immune response. Moreover, fatty skin folds can cause topical infections, ulcers, and delayed/impaired wound healing. Therefore, inflammatory and pro-inflammatory markers in the serum have gained importance in diseases such as diabetes and obesity. Furthermore, in obesity, reactive oxygen species (ROS) lead to DNA damage. 8-oxo-dG, which is the primary product of DNA oxidation, can be detected in the serum, saliva, and urine, making it an ideal biological marker for DNA damage in large population-based studies. The Comet assay analysis is a method used to demonstrate the double-strand breaks in DNA. Induction of γ-H2AX in tissue indicates the initiation of a well-regulated mechanism to reverse double-strand breaks in DNA. Potential benefits of monitoring the genomic health in obesity include creating a sense of urgency for personalized intervention measures and evaluating their progress. DNA damage in obesity is believed to be a reversible condition. Chronic inflammation is an etiological factor known to support DNA damage and neoplastic transformations in cells. Cytokines secreted from adipose tissue, especially TNF-alpha, IL-6, and IL-1β, promote the accumulation of various cells, including neutrophils, macrophages, and dendritic cells, and it indicates the initiation of an inflammatory process. In this project, it was aimed to investigate possible changes in inflammation markers and DNA damage in individuals undergoing bariatric surgery, who were beginning to improve endocrine and metabolic syndrome markers. 
 Materials and methods: For this purpose, blood and urine samples were collected from 45 obese patients, who had undergone bariatric surgery and 45 healthy volunteers matched for age and gender. The levels of inflammatory markers (IL-1β, IL-6, IL-8, and TNF-α) and the DNA damage marker γ-H2AX in serum, as well as the amount of 8-oxo-dG in urine, were determined using ELISA. Additionally, the percentage of DNA damage was determined using the Comet assay analysis. 
 Results: Weight control achieved through bariatric surgery and the subsequent reduction in fat tissue resulted in a significant decrease in the levels of γ-H2AX and 8-oxo-dG, as well as a parallel significant reduction in the percentage of DNA damage in the Comet assay results. The significant decrease in inflammatory markers IL-1β, IL-6, IL-8, and TNF-α levels indicated that bariatric surgery also affects inflammation indirectly. 
 Conclusion: Although there are numerous studies in the literature on individual parameters related to DNA damage in various diseases and obesity, it is believed that the present study determining DNA damage, oxidation, and repair mechanisms simultaneously with inflammatory marker levels serves as a guiding example for comparing genomic health and stability in pre-obese, post-obese, and non-obese individuals.

One Anastomosis Gastric Bypass Surgery: Consequences Over Diabetic Parameters

Introduction: Excessive weight gain in individuals leads to various metabolic disorders, such as diabetes mellitus, contributing to a further increase in body mass index (BMI). Thus, the patient enters a vicious cycle that leads to irreversible health damage. Bariatric surgery has displayed positive outcomes of weight loss with the return of BMI towards normal, which may reduce blood glucose levels to near normal. The remission of diabetes mellitus may be attributed to the reduction in inflammation, improvement of insulin resistance, lowering of peptide YY, and overall improved metabolic state of the body.
 Methods: One fifty patients, both female and male, in the age group of 20-60 years with grade II and grade III obesity having mean BMI of 45.63±6.54 (male) and 41.81± 5.93kg/m2 (female) were randomly selected for this study. Hemoglobin, Fasting Blood sugar (FBS), 2 hours postprandial blood sugar (PP2BS). Hemoglobin A1c (HbA1c) serum insulin was assessed at the visit, marked as a baseline, then again at the visit 3 months, and finally at the visit by the patient 6 months after bariatric surgery.
 Results: Hemoglobin level increased significantly from baseline at the 3rd-month post-surgery visit. FBS increased substantially from baseline at the 3rd-month postsurgery visit, which decreased considerably at the 6th-month visit following surgery. HbA1c showed a significant decrease in level from baseline following surgery.
 Conclusion: Improvement in BMI following bariatric surgery may have a positive impact on blood glucose levels in diabetic patients who may hope to see better management of their condition and may enjoy a better quality of life.
 Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 29-38

Eco-friendly Nanoparticles Synthesized from Salvia sclarea Ethanol Extract Protect against STZ-induced Diabetic Nephropathy in Rats via Antioxidant, Anti-inflammatory, and Apoptosis Mechanisms.

Recent global scientific attention has been directed towards eco-friendly synthesis and versatile applications of silver nanoparticles (AgNPs) due to their effectiveness against specific cells and tissues. This study aimed to develop a green synthesis method for AgNPs using ethanolic extract from Salvia sclarea aerial parts, and to assess their protective efficacy against streptozotocin (STZ)-induced diabetic nephropathy in rats. Additionally, antioxidant, anti-inflammatory, and apoptosis studies were conducted to understand their mode of action. Characterization via ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and X-ray diffraction (XRD) confirmed the formation of ethanol extract of Salvia sclarea silver nanoparticles (EESS AgNPs), with a distinctive absorption peak at 400 nm. Scanning electron microscopy (SEM) analysis revealed predominantly spherical and quasi-spherical shapes of the synthesized nanoparticles. The treatment procedure spanned for a period of 12 weeks in diabetic rats and were evaluated for inflammatory markers (tumor necrosis factor-α, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) and apoptosis markers (Bcl-2, Bax, cleaved-caspase-3). Results demonstrated that treatment with EESS AgNPs significantly reduced blood glucose levels compared to the diabetic group. Additionally, EESS AgNPs treatment led to a significant decrease in levels of pro-inflammatory cytokines TNF-α, IL-1β, and PKC-ꞵ in renal cells. Furthermore, EESS AgNPs effectively modulated antioxidant enzyme concentrations, including GSH, SOD, GPx, and CAT, bringing them to acceptable levels. Administration of EESS AgNPs also resulted in a significant decrease in protein levels of Bax and activated caspase-3, while increasing expression of the anti-apoptotic protein Bcl-2 in renal cells of STZ-induced diabetic rats. In conclusion, EESS AgNPs demonstrate potent anti-hyperglycemic effects, potentially mitigating diabetic nephropathy by suppressing hyperglycemiainduced oxidative stress, apoptosis, and inflammation in renal cells of diabetic rats.

Therapeutic and diagnostic complex in intestinal failure syndrome in patients with closed abdominal trauma

Improving treatment outcomes in patients with closed abdominal trauma through comprehensive diagnosis of SCN and optimization of enteral therapy in patients with closed abdominal trauma. The study included 40 patients (29 (72.5%) men and 11 (27.5%) women), who underwent examination and treatment at the State Budgetary Institution "Research Institute of SP. Im. N.V. Sklifosovsky Research Institute of St. Petersburg State Medical Center with the diagnosis: Closed abdominal trauma. The age of the patients varied from 25 to 81 years (Mean age was 49.6±13.1). To evaluate the effectiveness of intensive therapy, the patients were divided into 2 groups: the comparison group (n=26) included patients who were treated with complex conservative therapy. Patients of the main group (n=14) conservative therapy was supplemented with the use of ER to restore the functional activity of the intestine under the control of ultrasound and assessment of the degree of intra-abdominal hypertension, as well as with Intestamine to stimulate the intestinal trauma. In the course of the study it was found that, as a result of complex enteral therapy in the patients of the main group, starting from the 7th day of stay in the ORIT, positive dynamics was observed, consisting in a statistically significant decrease in the levels of lactate, ALT, AST, LDH, and CRP. By the 14th day there was also a statistically significant decrease in leukocyte and PCT levels. The lethality in the main group amounted to 7.2%, n=1. At the same time, in patients of the comparison group only by the 7th day there was a decrease in concentration of CRP (p=0.065), by the 10th day - ALT (<0.001) and by the 14th day there was a decrease in leukocytes level (p=0.038). Lethality in this group amounted to 23.1%, n=6. Timely initiation of pathogenetic enteral therapy contributes to faster normalization of clinical and laboratory parameters, protection of intestinal barrier function, prevention of complications associated with bacterial translocation and bacterial overgrowth syndrome, increase in immunoresistance of the organism.

Promene b2-mikroglobulina i elektrolita u različitim stadijumima HOBP i njihova vrednost u proceni prognoze

Background: To investigate the changes of b2-microglobulin and electrolyte in different stages of chronic obstructive pulmonary disease (COPD) and the value of evaluating prognosis. Methods: A retrospective study was undertaken on 120 patients diagnosed with COPD and treated at our respiratory department between February 1, 2020, and January 31, 2023. These patients were classified into three groups based on the GOLD classification: mild (FEV1 &gt; 81%), moderate (51% &lt; FEV1 ≤ 80%), and severe (FEV1 ≤ 50%). As a control group, 40 healthy individuals who had routine examinations during the same period were selected. The COPD patients were then followed up and divided into a good prognosis group (n = 67) and a poor prognosis group (n = 53). The levels of b2-microglobulin and electrolytes were measured in patients with different stages of the disease and different prognoses. Kendall's tau-b and ordered logistic regression were employed to analyze how the changes in b2-microglobulin and electrolyte levels correlated with disease severity. Furthermore, the prognostic value of b2-microglobulin and electrolyte levels in COPD was assessed using an ROC curve. Results: In comparison to the control group, the severity of COPD patients displayed a notable increase in b2microglobulin levels, while there was a significant decrease in levels of calcium, chlorine, potassium, and sodium. Kendall's tau-b correlation coefficient analysis indicated a positive correlation between COPD severity and b2microglobulin, and a negative correlation between COPD severity and levels of calcium, chlorine, potassium, and sodium. Logistic regression analysis revealed that there was a positive correlation between disease severity and b2microglobulin, and a negative correlation between disease severity and levels of calcium, chlorine, potassium, and sodium. Furthermore, the poor prognosis group exhibited a significant increase in b2-microglobulin levels, alongside a significant decrease in levels of calcium, chlorine, potassium, and sodium compared to the good prognosis group (P &lt; 0.05). ROC curve analysis demonstrated that a combined detection of b2-microglobulin, calcium, chlorine, potassium, and sodium yielded significantly higher area under the curve, sensitivity, and specificity values compared to single detection methods, highlighting its significant predictive value for COPD prognosis. Conclusions: Patients who presented with a more severe form of the disease exhibited elevated levels of b2microglobulin and reduced electrolyte levels. Prognostic accuracy was significantly enhanced when b2-microglobulin and electrolyte levels were analyzed together, offering a superior method for predicting patient outcomes.

Effect of exercise training on Type 2 diabetes management and lipid profile

Objective: To evaluate the effect of exercise training on glycemic control and levels of lipid among diabetic patients. Methodology: This randomized controlled trial (RCT) was conducted in Upper Nile University, Sudan from January 2022 to April 2023. It was registered on Iranian Registry of Clinical Trials (the registration reference is IRCT20230827059278N1). Forty patients with type 2 diabetes mellitus were allocated to the intervention group from the Jaber Abuelez Diabetic Center and Sameer Primary Healthcare Center, and the control group was taken from Tooty Primary Healthcare Center and Shambat Primary Healthcare Center. For a whole year, the intervention group had exercise instruction. Lipd profile and HgA1c were assessed before and after the exercise training to evaluate the effect. SPSS was used to analyze the data. Results: Exercise training resulted in a significant decrease in levels of triglycerides (-42.11, p&lt;0.05), LDL (-8.92, p&lt;0.05), HDL (+4.5 for males and +8.96 for females, p&lt;0.05), and HbA1c (mean difference: -0.6, p&lt;0.01). There was a significant reduction in LDL (-10.22, p&lt;0.05), HbA1c (-0.69, p&lt;0.05), and triglycerides (-33.07, p&lt;0.01). Conclusion: The exercise training is a useful strategy for maintaining lipid profiles and controlling blood sugar in patients with type 2 diabetes.

The effects of curcumin on hepatic T2*MRI and liver enzymes in patients with β-thalassemia major: a double-blind randomized controlled clinical trial.

Background: Curcumin present in turmeric has been considered due to its cancer-preventive features, antioxidant and anti-inflammatory properties. This double-blind, randomized, controlled clinical trial with a reasonable sample size and longer intervention period was conducted to investigate how oral curcumin affected cardiac and hepatic T2*MRI and liver enzymes in patients with β-thalassemia major. Method: This clinical trial study was conducted on 171 patients over 5 years old. The subjects were randomly divided into a curcumin-treatment group and a placebo group to receive either curcumin capsules twice daily or placebo for 6 months. Patients were examined once a month for 6 months to receive capsules and measure the levels of alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), direct and total bilirubin, ferritin and cardiac and hepatic T2*MRI. Result: There was a significant decrease in levels of AST, ALT, ALP, and bilirubin (direct and total) in the curcumin group compared with the placebo group by the end of the study (p < 0.05). The levels of serum ferritin remained unchanged in both groups at the end of the follow-up period (p > 0.05). No significant differences were observed between the curcumin and placebo groups at baseline values or at the end of the study of cardiac and hepatic T2*MRI and serum magnesium. Conclusion: Administration of curcumin has some beneficial effects on liver function by reducing liver enzymes in patients with beta-thalassemia major.

Влияние металлокомплекса С10H14CuO4 на выживаемость, цитогенетические показатели и показатели крови животных с ожогами III-АВ степени

One of the priority tasks of modern medicine is the search for new effective means that contribute to the treatment of burn injuries. In this area, organometallic complexes based on copper are of particular interest. The aim of the work is to evaluate the possible beneficial effects of the С10H14CuO4 metal complex on thermal burns by determining toxicity, analyzing survival rate and some cytogenetic and blood parameters. The С10H14CuO4 metal complex turned out to be a low-toxic compound: the LD50/7 value was 1815 mg/kg. The study of survival rate, blood values and cytogenetic parameters showed a beneficial effect of the C10H14CuO4 metal complex. Studies have shown that in the early stages after the burn and injection of the complex in animals injected with the compound C10H14CuO4, there is a significant decrease in blood clotting time and hematocrit level, an increase in the number of leukocytes. There is also a significant decrease in the levels of platelets, erythrocytes and hemoglobin. By the end of the experiment, there was a trend towards normalization of hematological parameters. The dynamics of the survival rate of animals from the group "burn + injections of the metal complex" is presented, with the corresponding regression curve and an equation that allows, by extrapolation, to predict changes in the percentage of long-term survival of the experiment. In the “burn + С10H14CuO4” group, the processes of wound healing, epithelialization, hair growth are more intense than in the pure burn group, which indicates the beneficial effect of this metal complex on the burned organism.

Effect of Pimpinella tirupatiensis Extract on Brain Free Radical Toxicity in STZ Induced Diabetic Rats

The objective of this study was to investigate the effects of Pimpinella tirupatiensis on oxidative stress markers in different regions of the brain (cerebral cortex, cerebellum, hippocampus, and Pons medulla) in rats with diabetes. Diabetes was induced in wistar rats by injecting them with STZ (40 mg/kg). The rats were then administered Pimpinella tirupatiensis aqueous extract (750 mg/kg / b.w. /day) and glibenclamide (Glb) (20 mg/ kg / b.w. /day) orally for 30 days. After 4 weeks of high blood sugar, the activity of antioxidant enzymes was measured in both the diabetic and control groups. Diabetes can worsen nerve damage and cause oxidative damage due to high blood sugar levels. The diabetic rats displayed a significant decrease in levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and reduced glutathione. However, when ginger was administered orally, it enhanced the activity of antioxidant enzymes in the diabetic rats. This suggests that Pimpinella tirupatiensis has a protective effect on the brain by enhancing antioxidant defense mechanisms in diabetic rats. Furthermore, it has a neuroprotective effect by enhancing the brain's antioxidant defense mechanisms and thereby attenuating the progression of hyperglycemia and some complications caused by diabetes in the rat brain.

Antioxidant and Antiatherogenic Responses of Black Solo Garlic in Alloxan-Induced White Rats

The association between the consumption of black solo garlic (SG) and the increase in antioxidant enzymes and the ability to prevent atherogenicity has not been studied much. This study aims to examine the antioxidant and antiatherogenic capacities of black solo garlic in aloksan induced rats. This study used a true experimental design with a pre- and post-test approach with a control group design. The sample of 30 Wistar rats was randomly divided into 6 groups: a healthy control, a negative control, treatment at doses of 6.5, 13.5, and 26 g/KgBW, and positive controls receiving vitamin C at a dose of 1 g/kgBW. The outcomes demonstrated that following the induction, MDA, CRP, LDL, and IL-6 levels increased, while SOD and GSH-Px enzyme levels decreased. After treatment with black solo garlic for 14 days, there was an increase in the enzymes SOD and GSH-Px, as well as a significant decrease in levels of MDA, IL-6, CRP, and LDL in experimental animals. The SG dose of 13.5 g/kg BW is the most effective dose in this study. The active compounds in SG function as antioxidants in preventing atherogenic events.

To Evaluate the Hepatoprotective Activity of Leaves of Salacia Chinensis Linn. on CCl4 Induced Albino Wistar Rats

The main aim of the present study is to evaluate the Hepatoprotective activity of aqueous slurry of leaves of Salacia chinensis Linn .on CCl4 induced liver damage in rats. Hepatotoxicity was induced by CCl4 and the biochemical parameters such as serum glutamate pyruvate transminase (sGPT), serum glutamate oxaloacetate transaminase (sGOT), alkaline phosphatase (sALP), Blood glucose level, Liver glycogen level and histopathological changes in liver were studied along with silimarin as standard Hepatoprotective agents. The Phytochemical investigation of the aqueous slurry showed significant decrease in the levels of sGPT, sGOT, sALP as compared to the animals treated with Silimarin, a known, standard hepatoprotective agent. A significant decrease in blood sugar level and liver glycogen was also observed in the animals treated with aqueous slurry of leaves of Salacia chinensis Linn.

Possible association of primary open-angle glaucoma with thyroid dysfunction and oxidative stress

Background Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Thyroid dysfunction and oxidative stress can be associated with POAG. Purpose The aim of this study was to determine whether thyroid dysfunction (hypothyroidism or hyperthyroidism) is associated with glaucoma in Egyptian patients and to evaluate the level of oxidative stress (OS) markers in the serum of POAG patients. It also aimed to investigate the relationship between the OS markers and thyroid hormones in those patients. Patients and methods The study included 60 patients with POAG who were compared with 20 normal controls. Serum samples from the POAG patients and controls were examined for thyroid hormones [triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH)] using the ELISA technique. The OS markers [hydrogen peroxide (H2O2), nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH)] were also determined using colorimetric methods. Results There were no significant differences in the levels of T4 and TSH in the patients (3.14±2.25 ng/dl and 2.43±1.37 u/l, respectively) compared with the controls (3.35±1.88 ng/dl and 1.76±0.99 u/l, respectively) (P=0.245 and 0.064, respectively). However, there was a significant decrease in the T3 level in the POAG patients (2.88±0.54 pg/ml) compared with the controls (3.35±0.6 pg/ml) (P=0.029). In addition, there was a significant increase in the levels of H2O2 (2.83±1.66 mM/l), NO (54.64±29.21 umol/l), and MDA (164.12±96.5 nmol/ml) in the patients compared with the controls (0.83±0.55 mMol/l, 22.49±6.37 umol/l, and 44.36±12.59 nmol/ml, respectively) (P&lt;0.001). There was also a significant decrease in the level of GSH in patients (54.32±32.1 mg/dl) compared with controls (103.99±45.52 mg/dl), (P&lt;0.001). A significant negative correlation was detected between TSH and T4 (r=−0.41, P= 0.001), TSH and MDA (r=−0.27, P=0.04), T3 and H2O2 (r=−0.05, P=0.05), and T4 and NO (r=−0.35, P=0.01). Conclusion There was no association between POAG and thyroid dysfunction. However, the POAG patients are susceptible to OS and damage, as they had elevated serum levels of H2O2, NO, and MDA and reduced levels of GSH. Since the thyroid hormone level was associated with the OS markers, antioxidant therapy may be beneficial and may help to regulate the intraocular pressure and protect the trabecular meshwork cells from OS in those patients.

Ameliorative effect of nebivolol in doxorubicin-induced cardiotoxicity.

This study aimed to investigate the potential of nebivolol in preventing doxorubicin-induced cardiotoxicity by targeting the inflammatory, oxidative, and apoptotic pathways. Twenty-eight male rats were randomly divided into four groups, each consisting of seven rats. The control group received standard diets and unrestricted access to water. The rats in the normal saline (N/S) group were administered a 0.9% normal saline solution for two weeks. The doxorubicin group (the "induced group") received doxorubicin at a dosage of 2.5 mg/kg three times per week for two weeks. The nebivolol group received an oral dose of 4 mg/kg of nebivolol for the same duration. The cardiac tissues of rats treated with doxorubicin exhibited increased levels of tumor necrosis factor, interleukin-1, malondialdehyde, and caspase-3 compared to the normal saline control group (p<0.05), along with decreased levels of total antioxidant capacity and Bcl-2. These results show that doxorubicin is harmful to the heart. The administration of nebivolol significantly reduced the cardiotoxic effects induced by doxorubicin, as indicated by a statistically significant decrease in the levels of inflammatory markers, specifically tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) (p<0.05). The nebivolol group exhibited a significant decrease in malondialdehyde levels, which serves as a signal of oxidation, in cardiac tissue compared to the doxorubicin-only group (p<0.05). Additionally, the nebivolol group showed a significant increase in overall antioxidant capacity. Nebivolol dramatically attenuated doxorubicin-induced cardiotoxicity in rats, likely by interfering with oxidative stress, the inflammatory response, and the apoptotic pathway.

Effects of Ramadan intermittent fasting on gut microbiome: is the diet key?

Much research has been conducted regarding the impact of diet on the gut microbiota. However, the effects of dietary habits such as intermittent fasting are unclear. This study aimed to investigate the effect of intermittent fasting during Ramadan on the gut microbiota. The study was conducted on 12 healthy adult individuals who practiced fasting 17 h per day for 29 consecutive days during the month of Ramadan. To determine the dietary intake of individuals, a 3-day dietary record was kept at the beginning and end of the study. Reads that passed quality filtering were clustered, and custom-prepared 16S rRNA gene regions of bacteria associated with the human microbiome were used as a reference. Consensus sequences were created, and genus-level taxonomic annotations were determined using a sequence identity threshold of 95%. The correlations between the dietary intake measurements of the participants and the respective relative abundance of bacterial genera were investigated. The results showed that Firmicutes were higher in abundance in the gut microbiota before fasting among participants, while they were significantly lower in abundance at the end of Ramadan fasting (p < 0.05). Proteobacteria were significantly higher in abundance at the end of the month of Ramadan (p < 0.05). Fasting was associated with a significant decrease in levels of seven genera: Blautia, Coprococcus, Dorea, Faecalicatena, Fusicatenibacter, Lachnoclostridium, and Mediterraneibacter. Conversely, the abundances of two bacterial genera were enhanced at the end of the fasting month: Escherichia and Shigella. The results of the dietary intake analysis showed that a negative correlation was detected for three comparisons: Ihubacter and protein (rho = -0.54, p = 0.0068), Fusicatenibacter and vegetables (rho = -0.54, p = 0.0042), and Intestinibacter and nuts (rho = -0.54, p-value = 0.0065). The results suggest that even when the fasting period during Ramadan is consistent, the types of food consumed by individuals can affect the gut microbiota.

Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients

BackgroundPatients with heart failure were affected severely by COVID-19. Most heart failure patients are on guideline directed medical therapy, which includes ACE inhibitors (ACEI) and ARBs. These medications were controversial at the beginning of the pandemic due to their interplay with the receptor that SARS-CoV-2 binds in the lungs. We investigated the effect that ACEI and ARB had on patients with hypertension, coronary artery disease, and heart failure. MethodsWe recruited 176 patients with COVID-19 infection and cardiovascular comorbidities at the American University of Beirut Medical Center in Lebanon. Of these, 110 patients were taking ACEI or ARB and 66 were not. We collected clinical data and looked at inflammatory markers such as CRP and IL-6 and cardiac markers such as troponin T. We also reported the incidence of ARDS, sepsis, and death of each patient, and compared the 2 groups. ResultsWe found that patients taking ACEI and ARB had a statistically significant decrease in levels of troponin T, IL-6, and CRP compared to patients not taking these medications (p < 0.05). We found no difference in rates of ARDS, sepsis, or death between the 2 groups. ConclusionInhibition of the renin-angiotensin-aldosterone-system had no effect on the mortality of patients with COVID-19 and on their overall disease progression. However, it may be beneficial not to stop these medications as they decrease inflammation in the body and the levels of troponin, which are related to increased stress on the heart.

Structure Activity Relationship and Molecular Docking of Some Quinazolines Bearing Sulfamerazine Moiety as New 3CLpro, cPLA2, sPLA2 Inhibitors.

The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative 3 was formed when compound 2 was treated with sulfamerazine. Also, compound 3 was reacted with NH2-NH2 in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative 4 was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and/or diethyl oxalate to produce quinazoline derivatives 5, 6, and 12, respectively. The results of the pharmacological study indicated that the synthesized 4-6 and 12 derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC50 values of the target compounds 4-6, and 12 against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 µM, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 µM, respectively. The IC50 values of the target compounds 4-6, and 12 against sPLA2 were 2.84, 2.73, 1.016, and 4.45 µM, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 µM, respectively. The IC50 values of the target compounds 4-6, and 12 against cPLA2 were 1.44, 2.08, 0.5, and 2.39 µM, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 µM, respectively. Also, incubation of lung cells with LPS plus derivatives 4-6, and 12 caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-α, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds 2-6 and 12 and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds 2-6 and 12 with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound 6 is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound 6 was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC50 value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 µM, indicating that it has low effectiveness.

Coq10 for preventing cardiotoxicity in breast cancer patients treated with trastuzumab.

Trastuzumab is a successful treatment option for HER2-positive breast cancer, but a decline in left ventricular ejection fraction (LVEF) and an increase in inflammatory and cardiac enzyme biomarkers can lead to cessation and termination of therapy. This study aimed to investigate the ability of Coenzyme Q10 (Coq10) to avoid these adverse effects. The study included 100 female patients with HER2+ (HER2+3 or amplified gene) breast cancer. All patients underwent standard adjuvant chemotherapy regimens, which involved a four-cycle treatment of Adriamycin, Cyclophosphamide, Docetaxel, and an initial 8 mg/kg loading dose of trastuzumab, followed by a year of 6 mg/kg maintenance doses every three weeks. One group of 50 patients received trastuzumab and a placebo, while the other 50 were given trastuzumab and CoQ10 for a full year. The CoQ10-treated group exhibited a statistically significant decrease in levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL6), soluble toll-like receptor 4 (sTLR4), and cardiac troponin I (cTnI) compared to the control group (p<0.05). However, there was no significant difference in the mean F2-isoprostane levels between the treated and the control groups at any data collection point. Furthermore, the CoQ10-treated group experienced a significant reduction in the decline of EF levels compared to the control group at all stages except for baseline. According to our findings, Coenzyme Q10 protected patients with HER2+3 breast cancer from the cardiotoxicity of trastuzumab by increasing ejection fraction and decreasing inflammatory biomarkers and cardiac enzyme levels.

Vitamin D supplementation reduced blood inflammatory cytokines expression and improved graft function in kidney transplant recipients.

Chronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection). A retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant. Compared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1β, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P <0.05). The supplementation of vitamin D effectively increased the serum concentration of vitamin D in kidney transplant recipients (KTRs) in the treated group. During the course of treatment, the treated group exhibited a gradual increase in eGFR levels, which were significantly higher than those observed in the untreated group at 12 months post-transplant (p<0.05). Notably, as eGFR improved, there was a significant decrease in levels of IL-1β, IFN-γ, IL-2, IL-10, IP-10 and HMGB1 in the treated group compared to the untreated group (P<0.05). This study confirmed that immune-inflammation is a crucial factor in the development of CAD in KTRs.VD deficiency impairs its anti-inflammatory activity. By assisting in the regulation of excessive immune inflammation and restoration of immune homeostasis, effective VD supplementation contributes to protection and maintenance of graft function in KTRs.

Effects of Alcoholic Extracted and Dry Eggplant (Solanum Melongena) on Hyperlipidemia Treatment in Rats

This study was carried out to investigate the potential of crude ethanolic extracts of eggplant (Solanum melongena) peels, fruit, and seeds, as well as dry eggplant, in the treatment of hyperlipidemia in rats. Forty-nine adult female Sprague Dawley rats were used with a weighting between (280-340) grams. Following the establishment of hyperlipidemia by providing them with a high-fat diet consisting of 4% cholesterol with 5% egg yolk for a period of 30 days in all groups except the control negative. Afterward, the rats were divided into seven groups of 7 rats as followed: The first group control negative was given standard pellets and water only, and the second group control positive induction hyperlipidemia this applied to all groups. Other groups (third, fourth, and five) were administered with alcoholic extracts of Solanum Melongena parts including the peel group, fruit group, and seed group, at a dose of 400 mg/kg/B.W. orally once a day, and group six received dry eggplant without extract at a dose of 200 mg/kg/diet once daily. The seven groups received atorvastatin at a dose of 20 mg/ B.W. orally once daily for a period of 45 days for all groups. The results of the study on serum lipid profile in rats indicated that the peel and atorvastatin groups exhibited a significant decrease in levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and low-density lipoprotein (VLDL). Furthermore, the peel and atorvastatin groups had substantially elevated high-density lipoprotein (HDL) levels. The study suggests that eggplant peel extract and atorvastatin, a common drug, can potentially treat hyperlipidemia in rats.