The amelioration effect of antidiabetic agents on cytokine expression in patients with type 2 diabetes mellitus.

Inflammation is a condition that is closely linked to diabetes mellitus type 2 (T2DM), short for T2DM several different antidiabetic medications have been produced to regulate hyperglycemia, with indications that these therapies may have anti-inflammatory effects along with their glucose-lowering efficacy. Thus, this research was planned to explore the impact of antidiabetic agents on the cytokine expression levels -interleukin (IL)-1ß, IL-6, IL-17, and IL-37 when patients have T2DM. In this study, 168 eligible subject matter was split into two groups: 50 healthy individuals and 118 cases with T2DM, who were classified into two subgroups: 30 untreated patients and 88 patients treated with metformin-based therapy. The outcome exhibited a significant increase within HbA1c% and proinflammatory cytokines (i.e., IL-1ß, IL- 6, and IL-17), whereas IL-37 decreased considerably in untreated cases with T2DM compared to those in subjects who are healthy. Furthermore, the results showed increased levels Regarding waist size, body mass index and assessment using that homeostasis model, cholesterol, triglycerides, low-density lipoprotein levels, and heart danger elements in untreated cases with T2DM in comparison with hygienic subjects. Notably, treated patients with T2DM revealed an ameliorative impact on HbA1c, IL-6, IL-17, IL-37, IL-1ß levels and lipid profile compared with untreated patients with T2DM. Antidiabetic agents may have a beneficial activity on the inflammatory status by reducing blood glucose levels, hyperlipidemia, and proinflammatory cytokines. The anti-inflammatory activity of IL-37 can apply a potentially effective therapeutic goal in treating T2DM and its complications.

Relationship between Cytokines and Metabolic Syndrome Components: Role of Pancreatic-Derived Factor, Interleukin-37, and Tumor Necrosis Factor-α in Metabolic Syndrome Patients.

The metabolic syndrome (MetS) is a serious public health issue that affects people all over the world. Notably, insulin resistance, prothrombotic activity, and inflammatory state are associated with MetS. This study aims to explore the relationship between cytokines and tumor necrosis factor-α (TNF-α), pancreatic-derived factor (PANDER), and interleukin (IL-)-37 and the accumulation of MetS components. Eligible participants were divided into four groups as follows: group 1, patients with dyslipidemia; group 2, patients with dyslipidemia and obesity; group 3, patients with dyslipidemia, obesity, and hypertension; and group 4, patients with dyslipidemia, obesity, hypertension, and hyperglycemia. This study exhibited that serum levels of TNF-α and PANDER were significantly elevated (P < 0.001) in the MetS groups, while IL-37 level and IL-37 mRNA expression were significantly decreased (P < 0.001) relative to healthy controls. Moreover, this study has revealed significant correlations (P < 0.001) between MetS components and TNF-α, PANDER, and IL-37 levels in MetS patients. The aforementioned results suggested the association between the proinflammatory cytokine (TNF-α and PANDER) and anti-inflammatory cytokine (IL-37) with the accumulation of MetS components. Hence, the overall outcome indicated that PANDER and IL-37 may be considered novel biomarkers associated with increased risk of MetS and can be used as a promising therapeutic target in preventing, ameliorating, and treating metabolic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01079-z.

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action.

This study was designed to assess the ameliorative effects of eugenol and to propose the possible mechanisms of action of eugenol in diethylnitrosamine (DENA)/acetylaminofluorene (AAF)-caused lung cancer in Wistar rats. To induce lung cancer, DENA at a dose of 150 mg/kg body weight (b.wt) for 2 weeks were intraperitoneally injected once each week and AAF was administered orally at a dose of 20 mg/kg b.wt. four times each week for the next 3 weeks. DENA/AAF-administered rats were orally supplemented with eugenol at a dose of 20 mg/kg b.wt administered once a day until 17 weeks starting from the 1st week of DENA administration. Lung histological lesions, including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells, resulting from the DENA/AAF dosage, were ameliorated by eugenol treatment. However, a significant drop in the levels of LPO in the lungs and a remarkable rise in GSH content and GPx and SOD activities were observed in DENA/AAF-administered rats treated with eugenol compared with those in DENA/AAF-administered controls. Moreover, in DENA/AAF-administered rats, eugenol supplementation significantly reduced TNF-α and IL-1ß levels and mRNA expression levels of NF-κB, NF-κB p65, and MCP-1 but significantly elevated the level of Nrf2. Furthermore, the DENA/AAF-administered rats treated with eugenol exhibited a significant downregulation of Bcl-2 expression levels in addition to a significant upregulation in P53 and Bax expression levels. Otherwise, the administration of DENA/AAF elevated the protein expression level of Ki-67, and this elevation was reversed by eugenol treatment. In conclusion, eugenol has effective antioxidant, anti-inflammatory, proapoptotic, and antiproliferative properties against lung cancer.

The relationship between B-cell lymphoma 2, interleukin-1ß, interleukin-17, and interleukin-33 and the development of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is among the main complications of diabetes mellitus and has been a major factor of renal failure. This study was designed to address the association between beta-cell lymphoma-2 (Bcl-2), interleukin (IL)-1ß, IL-17, and IL-33 and the development of DN. METHODS: In this study, 20 healthy volunteers and 100 patients were enrolled. According to their biochemical markers, the patients were categorized into five groups: diabetic, chronic renal disease, diabetic chronic renal disease, end-stage renal disease, and diabetic end-stage renal disease. RESULTS: Our results showed a noticeable elevation in IL-1ß and IL-17 levels and a reduction in IL-33 and Bcl-2 levels in all investigated groups compared with those in the healthy group. Positive correlations were found between IL-1ß and fasting blood sugar and between creatinine levels and IL-17, HbA1c%, and sodium levels. However, negative correlations were found between IL-33 and urea and sodium concentrations and between Bcl-2 and HbA1c% and creatinine levels. CONCLUSIONS: The present data revealed a marked relationship between Bcl-2, IL-1ß, IL-17, and IL-33 levels and the onset and progression of DN. Understanding the molecular pathways of these processes could be translated into the development of therapeutic strategies.

Possible association of rotavirus IgG with cytokine expression levels and dyslipidemia in rotavirus-infected type 1 diabetic children.

BACKGROUND: Rotavirus (RV) has been postulated as a viral trigger for the onset of autoimmune disorders, such as type 1 diabetes (T1D). This study aimed to examine the conceivable association of RV IgG with cytokine levels and dyslipidemia in the pathogenesis of pediatric T1D. METHODS: This study included 30 healthy controls and 80 children with T1D who were divided into two groups based on the time since their T1D diagnosis: newly diagnosed (ND ≤ 1 year; n = 30) and previously diagnosed (PD > 1 year; n = 50). ND and PD patients were also separated into negative and positive according to IgG detection (RV IgG-, ND-, and PD-; RV IgG+, ND+, and PD+). RESULTS: Positive polymerase chain reaction for RVs was evidenced in 7.5% of children with T1D. Anti-RV IgG was 30% and 36% in ND and PD, respectively, compared to healthy controls (2 of 30, 6.6%; P < 0.05). Fasting blood sugar and hemoglobin A1c significantly increased in PD+ compared to PD-. Interferon-γ and interleukin (IL)-15 levels significantly increased. IL-12 and IL-22 mRNA expression was upregulated in ND+ patients compared to that in ND- patients. IL-37 mRNA expression was significantly downregulated in ND- and ND+ patients compared to that in healthy controls. Total cholesterol and high- and low-density lipoprotein-cholesterol levels were significantly lower in PD+ than in PD-; whereas triglyceride levels were higher than those in healthy controls. CONCLUSIONS: This study suggested that anti-RV IgG may have a role in the pathogenesis, development, and progression of T1D, and RV infections are implicated in dyslipidemia and inflammation status.

Novel strategies to oral delivery of insulin: Current progress of nanocarriers for diabetes management.

Diabetes mellitus is one of the most serious public health problems in the world. Repeated daily injections of subcutaneous insulin is the standard treatment for patients with type 1 diabetes mellitus; however, subcutaneous insulin injections can potentially cause local discomfort, patient noncompliance, hypoglycemia, failure to regulate glucose homeostasis, infections, and fat deposits at the injection sites. In recent years, numerous attempts have been made to produce safe and efficient nanoparticles for oral insulin delivery. Oral administration is considered the most effective alternative route to insulin injection, but it is accompanied by several challenges related to enzymatic proteolysis, digestive breakdown, and absorption barriers. A number of natural and synthetic polymeric, lipid-based, and inorganic nanoparticles have been investigated for use. Although improvements have recently been made in potential oral insulin delivery systems, these require further investigation before clinical trials are conducted. In this review, new approaches to oral insulin delivery for diabetes treatment are discussed, including polymeric, lipid-based, and inorganic nanoparticles, as well as the clinical trials performed for this purpose.

Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress.

Gestational diabetes mellitus (GDM) is a major pregnancy-related disorder with an increasing prevalence worldwide. GDM is associated with altered placental vascular functions and has severe consequences for fetal growth. There is no commonly accepted medication for GDM due to safety considerations. Actions of the currently limited therapeutic options focus exclusively on lowering the blood glucose level without paying attention to the altered placental vascular reactivity and remodelling. We used the fat-sucrose diet/streptozotocin (FSD/STZ) rat model of GDM to explore the efficacy of cinnamaldehyde (Ci; 20 mg/kg/day), a promising antidiabetic agent for GDM, and glyburide/metformin-HCl (Gly/Met; 0.6 + 100 mg/kg/day), as a reference drug for treatment of GDM, on the placenta structure and function at term pregnancy after their oral intake one week before mating onward. Through genome-wide transcriptome, biochemical, metabolome, metal analysis and histopathology we obtained an integrated understanding of their effects. GDM resulted in maternal and fetal hyperglycemia, fetal hyperinsulinemia and placental dysfunction with subsequent fetal anemia, hepatic iron deficiency and high serum erythropoietin level, reflecting fetal hypoxia. Differentially-regulated genes were overrepresented for pathways of angiogenesis, metabolic transporters and oxidative stress. Despite Ci and Gly/Met effectively alleviated the maternal and fetal glycemia, only Ci offered substantial protection from GDM-associated placental vasculopathy and prevented the fetal hypoxia. This was explained by Ci's impact on the molecular regulation of placental angiogenesis, metabolic activity and redox signaling. In conclusion, Ci provides a dual impact for the treatment of GDM at both maternal and fetal levels through its antidiabetic effect and the direct placental vasoprotective action. Lack of Gly/Met effectiveness to restore it's impaired functionality demonstrates the vital role of the placenta in developing efficient medications for GDM.

A novel layered double hydroxide-hesperidin nanoparticles exert antidiabetic, antioxidant and anti-inflammatory effects in rats with diabetes.

BACKGROUND: Incidence of diabetes has increased significantly worldwide over recent decades. Our objective was to prepare and characterize a novel nano-carrier of hesperidin to achieve a sustained release of hesperidin and to explore the potency of the novel formula as an antidiabetic agent compared to metformin in type 2 diabetic rats. METHODS: Hesperidin was loaded on MgAl-layered double hydroxide (LDH). The formula was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy, and dynamic light scattering. The release profile of hesperidin and MgAl-LDH-Hesperidin were studied in vitro. The parameters studied in vivo were blood glucose, glycated hemoglobin (HbA1c), insulin, lipid profile, and liver glycogen levels. We also investigated the levels of interleukin (IL)-17, tumor necrosis factor-Alfa (TNF-α), malondialdehyde (MDA), catalase, and the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and nuclear factor erythroid 2-related factor-2 (NrF2). RESULTS: There were variations in the XRD patterns and FTIR confirming the physical adsorption of hesperidin on the surface of LDH. The results indicated that the diabetic rats treated with administration of antidiabetic formula, MgAl-LDH-Hesperidin, showed a beneficial effect on the levels of blood glucose, insulin, HbA1c%, and lipid profile, comparing to diabetic control rats. The antidiabetic agent also showed a significant decrease in the levels of TNF-α, IL-17, and MDA, and an increase in the level of catalase. Marked upregulation of the expression levels of mRNA for PPARγ and NrF2 were recorded. CONCLUSION: The novel nano-hesperidin formula MgAl-LDH-Hesperidin revealed a sustained release of hesperidin and exhibited antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory properties, and also is a promising agent for effective delivery of drugs to treat type 2 diabetes.

Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes.

BACKGROUND: In type 1 diabetes mellitus (T1DM), cytokines have a central role in orchestrating multicellular relations between ß-cells and immune cells. This study aims to investigate the role of interleukin (IL)-21, IL-23, and IL-2, and their association with dyslipidemia in T1DM children. METHODS: The sample population consisted of 30 healthy controls and 70 children with T1DM, the latter of which were split into two groups according to the duration of their T1DM diagnosis: recent (≤ 1 year; n = 21) and older (> 1 year; n = 49) diagnoses. RESULTS: Fasting blood sugar and glycated hemoglobin levels in all diabetic children were significantly (P < 0.001) higher, whereas levels of plasma C-peptide were markedly (P < 0.001) lower in children with T1DM compared to healthy controls. In older T1DM diagnosis children, the levels of creatinine were noticeably (P < 0.05) increased relative to healthy controls. In all diabetic children, levels of total triglyceride, cholesterol, and low-density lipoprotein were increased significantly (P < 0.001) than those of healthy controls. Furthermore, the IL-21 and IL-23 mRNA expressions of all children with T1DM were elevated significantly (P < 0.001) relative to healthy controls, whereas IL-2 levels revealed a significant (P < 0.001) decrease in all diabetic children. CONCLUSION: There was a synergistic interplay between IL-21 and IL-23 with an antagonistic action of IL-2 in T1DM patients, and all three interleukins were associated with dyslipidemia in diabetic children. Importantly, therapies targeting IL-21 and IL-23 are promising targets for preventive strategies against the development of T1DM and its complications.

COVID-19 Pandemic and Male Fertility: Clinical Manifestations and Pathogenic Mechanisms.

The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency worldwide with over 118.27-million confirmed COVID-19 cases and 2.62-million deaths recorded, as of March 12, 2021. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur. Testis is the cornerstone of male reproduction, while reproductive health is the most valuable resource for continuity of the human race. Given the unique nature of SARS-CoV-2, the mechanisms of its impact on the testes have yet to be fully explored. Notably, coronaviruses have been found to invade target cells through the angiotensin-converting enzyme 2 receptor, which can be found in the respiratory, gastrointestinal, cardiovascular, urinary tract, and reproductive organs, such as testes. Coronavirus studies have suggested that testes might be a potential target for SARS-CoV-2 infection. The first etiopathogenic concept proposed by current hypotheses indicates that the virus can invade testes through the angiotensin-converting enzyme 2 receptor. Next, the activated inflammatory response in the testes, disease-associated fever, and COVID-19 medications might be implicated in testicular alterations. Although evidence regarding the presence of SARS-CoV-2 mRNA in semen remains controversial, this emphasizes the need for researchers to pay closer attention to sexually transmitted diseases and male fertility after recovering from COVID-19. In this review the latest updates regarding COVID-19-associated testicular dysfunction are summarized and possible pathogenic mechanisms are discussed.

Effect of Omeprazole on Osteoblasts and Osteoclasts in vivo and in the in vitro Model Using Fish Scales.

Omeprazole suppresses excessive secretion of gastric acid via irreversible inhibition of H+/K+-ATPase in the gastric parietal cells. Recent meta-analysis of data revealed an association between the use of proton pump inhibitors (PPIs) and increased risk of bone fractures, but the underlying molecular mechanism of PPI action remains unclear. In this study, we demonstrated that omeprazole directly influences bone metabolism using a unique in vitro bioassay system with teleost scales, as well as the in vivo model. The in vitro study showed that omeprazole significantly increased the activities of alkaline phosphatase and tartrate-resistant acid phosphatase after 6 h of incubation with this PPI. Expression of mRNAs for several osteoclastic markers was upregulated after 3-h incubation of fish scales with 10-7 M omeprazole. The in vivo experiments revealed that the plasma calcium levels significantly increased in the omeprazole-treated group. The results of in vitro and in vivo studies suggest that omeprazole affects bone cells by increasing bone resorption by upregulating expression of osteoclastic genes and promoting calcium release to the circulation. The suggested in vitro bioassay in fish scales is a practical model that can be used to study the effects of drugs on bone metabolism.

Hepatoprotective Effects of Polydatin-Loaded Chitosan Nanoparticles in Diabetic Rats: Modulation of Glucose Metabolism, Oxidative Stress, and Inflammation Biomarkers.

Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1ß mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.

The Impact of Glycemic Status and Metformin Administration on Red Blood Cell Indices and Oxidative Stress in Type 2 Diabetic Patients.

BACKGROUND: Most guidelines all over the world recommended metformin as the first-line treatment for in type 2 diabetic patients. Therefore, the present study was suggested to assess the outcome of metformin administration and glycemic status on alterations in red blood cell (RBCs) indices as well as the oxidative stress in type 2 diabetic patients. METHODS: Between December 2016 and October of 2017, a total of 158 eligible individuals were classified as 50 healthy subjects and 108 diabetic patients who were subdivided into six groups according to the type of anti-diabetic treatments. RESULTS: Overall, the results elucidated that hemoglobin concentration was markedly diminished, while red cell distribution width (RDW) value was significantly (P < 0.001) elevated in all diabetic groups as compared to control. Moreover, in all diabetic groups, malondialdehyde (MDA) concentration was elevated noticeably (P < 0.001), while reduced glutathione (GSH) revealed a lower concentration (P < 0.001) than that of control. CONCLUSION: The present study exhibited the amelioration effect of metformin administration on oxidative stress and glycemic status which reflected on some RBCs indices. However, hemoglobin concentration showed a noticeable diminution in all metformin-treated groups in spite of the improvement in glycemic and oxidative stress status which indicated that the metformin-induced anemia is independently from diabetic complications.

Retreatment Efficacy of Sofosbuvir/Ombitasvir/Paritaprevir/Ritonavir + Ribavirin for Hepatitis C Virus Genotype 4 Patients.

BACKGROUND: The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection. AIMS: To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens. METHODS: A total of 113 treatment-experienced patients were allocated for the completion of their treatment period. The enrolled patients were treated orally with SOF plus a fixed dose combination of OBV/PTV/r + RBV, which was administered orally based on the patients' tolerability. The primary end point was a sustained virological response (HCV RNA < 15 IU/mL), observed 12 weeks after the end of the treatment (SVR12). RESULTS: Among all patients, the treatment-experienced patients with SOF plus OBV/PTV/r + RBV had a higher SVR12 rate (97%; 109/113). Further, SVR12 was achieved by 98% (81/83) of non-cirrhotic patients and 93% (28/30) of cirrhotic patients. Additionally, the most common adverse events reported included fatigue, headache, insomnia, nausea, and dyspnea. CONCLUSIONS: The recent multi-targeted regimen of SOF plus OBV/PTV/r + RBV was well tolerated and achieved excellent SVR rates among retreatment-experienced Egyptian patients with prior DAA treatments failure, thus providing an alternative regimen for the retreatment of difficult-to-cure HCV GT4 patients.

Association between Antioxidant Enzyme Activities and Enterovirus-Infected Type 1 Diabetic Children.

OBJECTIVE: To examine the effect of infection with Enterovirus (EV) in children with type 1 diabetes (T1D) on the activities of serum antioxidant enzymes in diabetic and nondiabetic controls. SUBJECTS AND METHODS: Three hundred and eighty-two diabetic and 100 nondiabetic children were tested for EV RNA using reverse transcriptase (RT)-PCR. The activities of serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also estimated in diabetic patients infected with EV (T1D-EV+), those not infected with EV (T1D-EV-), and in nondiabetic controls. RESULTS: The frequency of EV was higher in diabetic children (100/382; 26.2%) than in healthy controls (0/100). Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and C-reactive protein (CRP) were significantly higher but C-peptide was significantly lower in diabetic children than in controls. CRP levels were higher in the T1D-EV+ group than in the T1D-EV- group, and higher in all diabetic children than in nondiabetic controls. The activities of the antioxidant enzymes GPx, SOD, and CAT decreased significantly in diabetic children compared to in controls. Moreover, the activities of the enzymes tested were significantly reduced in the T1D-EV+ group compared to in the T1D-EV- group. CONCLUSION: Our data indicate that EV infection correlated with a decrease in the activity of antioxidant enzymes in the T1D-EV+ group compared to in the T1D-EV- group; this may contribute to ß cell damage and increased inflammation.

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

The implication of miR-200a and miR-132 expression and their correlations with NF-κB/TNF-alpha signaling in adults with diabetic nephropathy.

Aim: The primary factor causing chronic renal failure is diabetic nephropathy (DN) worldwide. However, the current biomarkers for DN have limited diagnostic utility. Thus, this work aimed to clarify the implications of microRNA-200a (miR-200a) and microRNA-132 (miR-132) and their correlation with NF-κB (nuclear factor- kappa beta), and, TNF-α (tumor necrosis factor -alpha) signaling to identify biomarkers able to distinguish late-stage from early- stage DN. Methods: Fifty healthy controls, and 271 type 2 diabetic (T2D) patients (166 male plus 105 female) were enrolled. Participants were stratified into seven groups according to along with the estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c%), healthy controls, diabetes without DN (G1), diabetes with mild renal impairment (G2), and four DN grades (G3a, G3b, G4, and G5). Results: Compared to healthy controls, the DN groups exhibited linear increases in serum miR-200a, TNF-α, NF-κB, matrix metalloproteinase (MMP-9) and interleukin-6 (IL-6) levels and reductions in miR-132 serum expression. Among the patients, NF-κB and TNF-α produced a negative correlation with miR-132, while, positive correlation has been discovered with miR-200-a. The operating characteristic of the receiver curve (ROC), proved that, miR-200a also miR-132 had good diagnostic performance in distinguishing early from advanced DN. Conclusion: MiR-200a as well as miR-132 expression levels, and their correlations with NF-κB/TNF-alpha signaling, were able to differentiate between DN patients with lower eGFR, suggesting their utility as diagnostic and prognostic biomarkers.

Insights into the possible impact of COVID-19 on the endocrine system.

The novel 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible and pathogenic coronavirus. Because of the novelty of the COVID-19 pandemic, few data are available on the impact of the SARS-CoV-2 on the different endocrine glands. Previous studies of severe acute respiratory syndrome (SARS) have shown a harmful effect on endocrine function. Notably, the angiotensin-converting enzyme-2 receptor, which is the entry route of coronaviruses to the host cell, is widely expressed in the endocrine organs including testis, endocrine pancreas, thyroid, and adrenal, and pituitary glands. Clinical and biochemical manifestations have been recorded in COVID-19 patients resulting in changes in endocrine activities, which were also recorded during the SARS outbreak in 2003. This review aims to explore the impact of SARS-CoV-2 infection on the function of endocrine glands, based on the latest research in the field.

The protective impact of hesperidin against carbimazole-induced hypothyroidism, via enhancement of inflammatory cytokines, histopathological alterations, and Nrf2/HO-1.

The aim of this study was to evaluate the anti-inflammatory, antioxidant, and antiproliferative effects of hesperidin (HSP) and eltroxin (ELT) on hypothyroidism (HPO) induced by carbimazole (CBZ) in white male albino rats. Thirty-two adult rats were categorized into four groups: Group 1, no treatment (control); Group II, treated with CBZ (20 mg/kg); Group III, treated with HSP (200 mg/kg) + CBZ; and Group IV, treated with ELT (0.045 mg/kg) + CBZ. All treatments were provided as oral daily doses for 90 days. Thyroid hypofunction was significantly manifested in Group II. However, increased levels of thyroid hormones, antioxidant enzymes, nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and interleukin (IL)-10, and a decrease in the level of the thyroid-stimulating hormone were observed in Groups III and IV. On the contrary, decreased levels of lipid peroxidation, inducible nitric oxide synthase, tumor necrosis factor α, IL-17, and cyclooxygenase 2 were detected in groups III and IV. The histopathological and ultrastructural findings were ameliorated in Groups III and IV; on the contrary, Group II presented with significant increases in the height and number of layers of the follicular cells. Immunohistochemistry demonstrated a marked increase in thyroglobulin and significant decreases in the levels of nuclear factor kappa B and proliferating cell nuclear antigen in Groups III and IV. These results confirmed the effectiveness of HSP as an anti-inflammatory, antioxidant, and antiproliferative agent in rats with hypothyroidism. Additional studies are required to assess its potential as a novel agent against HPO.