Significant Decrease In Levels Research Articles

Peripheral-central network analysis of cancer cachexia status accompanied by the polarization of hypothalamic microglia with low expression of inhibitory immune checkpoint receptors

While the excessive inflammation in cancer cachexia is well-known to be induced by the overproduction of inflammatory mediators in the periphery, microflora disruption and brain dysfunction are also considered to contribute to the induction of cancer cachexia. Hypothalamic microglia play a crucial role in brain inflammation and central-peripheral immune circuits via the production of inflammatory mediators. In the present study, we evaluated possible changes in excessive secretion of gut microbiota-derived endotoxin and the expression timeline of several inflammation-regulatory mediators and their inhibiting modulators in hypothalamic microglia of a mouse model of cancer cachexia following transplantation of pancreatic cancer cells. We demonstrated that the plasma level of lipopolysaccharide (LPS) was significantly increased with an increase in anaerobic bacteria, especially Firmicutes, in the gut at the late stage of tumor-bearing mice that exhibited dramatic appetite loss, sarcopenia and severe peripheral immune suppression. At the early stage, in which tumor-bearing mice had not yet displayed “cachexia symptoms”, the mRNA expression of pro-inflammatory cytokines, but not of the neurodegenerative and severe inflammatory modulator lipocalin-2 (LCN2), was significantly increased, whereas at the late “cachexia stage”, the level of LCN2 mRNA was significantly increased along with significant decreases in levels of inhibitory immune checkpoint receptors programmed death receptor-1 (PD-1) and CD112R in hypothalamic microglia. In addition, a high density of activated neurons in the paraventricular nucleus (PVN) of the hypothalamus region and a significant increase in corticosterone secretion were found in cachexia model mice. Related to the cachexia state, released corticosterone was clearly increased in normal mice with specific activation of PVN neurons. A marked decrease in the natural killer cell population was also observed in the spleen of mice with robust activation of PVN neurons as well as mice with cancer cachexia. On the other hand, in vivo administration of LPS in normal mice induced hypothalamic microglia with low expression of inhibitory immune checkpoint receptors. These findings suggest that the induction of cancer cachexia may parallel exacerbation of the hypothalamic inflammatory status with polarization to microglia expressed with low levels of inhibitory immune checkpoint receptors following LPS release from the gut microflora.

Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

A cross talk study on sitagliptin mediated reclamation on TGF β signalling, DPP 4, miR-29a and miR-24 expression in PCOS rats fed with high fat-high fructose diet

Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive, endocrine and metabolic disturbance which is very commonly observed in females of reproductive age group. The disease is still incurable however the use of synthetic drugs in combination with lifestyle is recommended. Accordingly, the present study was conducted to investigate the possible beneficial effects of sitagliptin on PCOS induced rats on control diet (CD)/high fat- high fructose diet (HFFD). PCOS was induced by giving testosterone propionate (TP) for 28 days to both the CD/HFFD rats and treated with STG i.p. for last 15 days. At the end of the experiment lipid profile, inflammatory markers, expression of NF-κB-p65, miR-24 and miR-29a, fibrotic and apoptotic proteins from ovary tissue were examined. Moreover, lipid accumulation and fibrosis of ovary tissue was further confirmed using Sudan III and Masson’s trichrome stain. STG treated rats exerted a significant decrease in levels of cholesterol, TG, LDL-C, VLDL-C, IL-6 and TNF-α and increased HDL-C level, miR-24 and miR-29a expression. STG treated groups expressed significantly decreased expression of NF-κB-p65, TGF-β1, p-Smad 2 and p-Smad 3 followed by no significant changes in the expression of BAX, caspase-9, caspase-3 and Bcl-2 in all the PCOS induced groups. Among all the CD/ HFFD fed groups, rats on HFFD showed more devastating effect which suggests that diet plays a major role in genesis of PCOS. In conclusion, current results reflect the potential impact of STG against dyslipidaemia, inflammation and fibrosis in PCOS rats via regulating dyslipidaemia and fibrosis via DPP 4 mediated miR-29a expression.

The Effect of Infection with some Intestinal Parasites on some Immune Parameters

275 fecal samples were collected from visitors to Tikrit Teaching Hospital and some private laboratories in Tikrit city/Salah al-Din Governorate. The collection period lasted from December 2022 until April 2023. The study included examining samples of both males and females of different ages. The study showed a significant decrease in level of IgG among people infected with Entamoeba histolytica by 92.00 ± 19.1, as well as for people infected with Giardia lamblia, as a significant decrease was recorded by 76.43 ± 15.1 compared to healthy people by a percentage of 130.60 ± 29.5. No significant difference was recorded between people infected with E.histolytica in level of IgM, as the percentage reached 83.4 ± 13.6. Likewise, for people infected with G.lamblia, no significant difference was recorded, as the percentage was (106.0 ± 21.7) compared to healthy people, as the percentage reached ( 84.6 ± 18.0. ). There was a significant decrease in the level of the CD4 differentiation complex among people infected with E. histolytica by a rate of 160.8 ± 23.9. Likewise, for people infected with G. lamblia, a significant decrease was recorded, reaching a rate of 187.5 ± 31.8 compared to healthy people by a rate of 475.2 ± 28.1. A significant decrease was recorded among people infected with E. histolytica in the level of CD8 differentiation complex, as the percentage reached 9.00 ± 2.51. Likewise, for people infected with G. lamblia , a significant decrease was recorded by 10.18 ± 2.60 compared to healthy people, with a percentage of 14.50 ± 3.40. There was a significant decrease in the level of IL6 in people infected with E. histolytica, as the percentage reached 85.02 ± 13.20, while in people infected with G. lamblia, no significant difference was recorded, as the percentage reached 196.30 ± 17.10, compared to healthy people, with a percentage of 220.20 ± 23.20.

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

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<0.05), LDL (-8.92, p<0.05), HDL (+4.5 for males and +8.96 for females, p<0.05), and HbA1c (mean difference: -0.6, p<0.01). There was a significant reduction in LDL (-10.22, p<0.05), HbA1c (-0.69, p<0.05), and triglycerides (-33.07, p<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.

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.

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.

Changes in nasal, pharyngeal and salivary secretory IgA levels in patients with COVID-19 and the possibility of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms.

Although extensive research has been conducted on the role of local immunity in patients with SARS-CoV-2, little is known about the production and concentrations of secretory IgA (SIgA) in different mucosal compartments. This article aims to assess the secretion of SIgA in the nasal and pharyngeal compartments and saliva of patients with COVID-19 and to investigate the possibility and efficiency of correction of their secretion using combined intranasal and oral administration of a pharmaceutical containing antigens of opportunistic microorganisms. This study included 78 inpatients, aged between 18 and 60 years, who had confirmed COVID-19 with moderate lung involvement. The control group (n=45) received basic therapy, and the treatment group (n=33) was additionally administered the bacteria-based pharmaceutical Immunovac VP4 from day 1 to day 10 of hospitalization. SIgA levels were measured by ELISA at baseline and on days 14 and 30. No systemic or local reactions associated with Immunovac VP4 were reported. We observed a statistically significant reduction in the duration of fever and hospitalization in patients who received Immunovac VP4 compared with those from the control group (p=0.03 and p=0.05, respectively). Changes over time in SIgA levels in nasal swabs were found to be significantly different in the two treatment groups (F=7.9, p[78.0]<0.001). On day 14 of observation, patients in the control group showed a statistically significant reduction in SIgA levels from baseline (p=0.02), whereas patients in the Immunovac VP4 group had stable SIgA levels (p=0.07). On day 30 after the start of treatment, there was a statistically significant increase in SIgA levels in the Immunovac VP4 group compared with baseline (from 77.7 (40.5-98.7) μg/L to 113.4 (39.8-156.7) μg/L; p=0.05) and the levels measured on day 14 (from 60.2 (23.3-102.9) μg/L to 113.4 (39.8-156.7) μg/L; p=0.03). The control group showed a statistically significant decrease in levels of nasal SIgA (to 37.3) on day 30 (p=0.007 for comparison with baseline values and p=0.04 for comparison with levels measured on day 14). Changes over time in SIgA levels measured in pharyngeal swabs were also different between the two treatment groups, and this difference reached statistical significance (F=6.5, p[73.0]=0.003). In the control group, this parameter did not change throughout the study (p=0.17 for a comparison between the levels measured on day 14 and the baseline values, and p=0.12 for a comparison between the levels measured on day 30 and the baseline values). In the Immunovac VP4 group, there was a statistically significant increase from baseline in SIgA levels on study day 30: from 1.5 (0.2-16.5) μg/L to 29.8 (3.6-106.8) μg/L (p=0.02). Changes over time in salivary SIgA did not show a significant difference between study groups (F=0.3, p[66.3]=0.75). As part of combination therapy, the bacteria-based immunostimulant agent Immunovac VP4 increases SIgA levels in the nasal and pharyngeal compartments and induces clinical improvement. Induced mucosal immunity is central to the prevention of respiratory infections, particularly in patients with post-COVID-19 syndrome.