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Osteoporosis is a worldwide common disease characterised by reduced bone mass and increased risk of fractures.Many genetic variants are associated with the disease, but they account for only a small percentage of variance in individual bone mineral density and fragility fracture risk. Only recently have researchers recognised the role of a broad variety of environmental factors in the pathogenesis of osteoporosis, which has led to a further step: how genetic and environmental factors can interact, which is the next frontier in research on bone fragility.

Osteoporosis is a skeletal disease characterised by reduced bone mass and deterioration of bone microarchitecture, underlying a higher risk of fragility fractures. Several options are available for its treatment, including both anti-resorptive and anabolic agents. The present review discusses and summarises the most recent literature on anabolic treatment, with a focus on abaloparatide, and on the assessment of fragility fracture risk, with a focus on trabecular bone score. Finally, we provide a discussion on the effects of different antiosteoporotic medications in terms of fragility fracture risk reduction.

The extraordinary vaccination campaigns of the COVID-19 pandemic era put organizational and operational systems to the test in numerous territorial contexts. In the Veneto region, the activation of population vaccination centers (CVPs) guaranteed the provision of vaccines to mountain areas. These centers, drive-in and building-based, improved the efficiency of dose administration in relation to similar conditions where healthcare workers (HCWs) were routinely involved in clinics. Overall, a comparison of the two models investigated, with the same numbers of HCWs involved and the same opening hours for the vaccination sites, has shown that the CVPs are able to guarantee three times as many vaccines administered, compared with the traditional outpatient model. This study aims to provide a detailed analysis of the adopted organizational model, highlighting the best practices and improvements required to guarantee a timely and effective public health response, and evaluating the opportunities to deploy these innovative methods actively in a standard context.

Purpose: LRP5 high bone mass (HBM) is an autosomal dominant endosteal hyperostosis caused by mutations of the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Alternative names included "autosomal dominant osteosclerosis" and "Worth disease." The aim of the paper is to provide an historical overview of a disorder whose literature is complicated and confusing due to the past use of several denominations and lack of reviews., Methods: We collected case reports of HBM with evidence of autosomal dominant transmission preceding the identification of the LRP5 mutations in 2002 (Worth-type endosteal hyperostosis) and cases of LRP5 HBM confirmed by genetic analysis since 2002. The prevalence of relevant clinical and laboratory findings was estimated. We described an affected woman with neurological manifestations., Results: A 44-year-old Caucasian woman with torus palatinus complained of headache, hypo-/anosmia, and complete mixed deafness. Dual-energy X-ray absorptiometry (DEXA) scan revealed elevated bone mass. The A242T mutation of the LRP5 gene was detected. Including the present case, 155 patients have been reported to date. Neurological involvement and increased serum alkaline phosphatase (ALP) were present in 19.4% and 3.7% of cases, respectively. Facial changes and torus palatinus were observed in 61% and 41% of cases, respectively., Conclusions: We present the only historical review on Worth-type endosteal hyperostosis, now known as LRP5 HBM. Neurological manifestations, previously considered absent in the disease, affect 19.4% of the patients. Genetic analysis and appropriate denomination of LRP5 HBM are fundamental for diagnosis and to mitigate the confusion that has long characterized this disease., (© 2023. The Author(s).)

Objective: Systemic sclerosis (SSc) is burdened by Raynaud phenomenon (RP) and digital ulcers (DUs), and sometimes standard vasoactive therapies are ineffective or contraindicated. Selexipag is an oral selective IP prostacyclin receptor agonist approved for the treatment of SSc-related pulmonary arterial hypertension. We aimed to evaluate the clinical and instrumental efficacy of selexipag in SSc digital vasculopathy., Methods: Patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies were administered selexipag. RP- and DU-related clinical outcomes were evaluated, and digital perfusion was assessed by laser speckle contrast analysis (LASCA), all at baseline and after 3 months., Results: Selexipag was administered to 9 patients with SSc (66.6% female, mean age 52.3 [SD 16.6] yrs). One patient had to stop the drug because of adverse effects. After 3 months of selexipag administration, there was a significant reduction in RP daily episodes ( P = 0.01) and RP mean duration ( P = 0.04). The number of DUs decreased from 10 to 4 without reaching statistical significance. A significant improvement in mean perfusion of the fingers ( P = 0.02) was observed with LASCA., Conclusion: Selexipag showed good potential for the treatment of SSc digital vasculopathy. Our results are certainly preliminary, yet quite encouraging. New trials for the evaluation of selexipag efficacy in SSc digital vasculopathy are needed., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: To evaluate finger proximal-distal gradient (PDG) perfusion in subjects with primary Raynaud's phenomenon (PRP), then making comparisons with systemic sclerosis (SSc) patients and healthy controls (HC)., Methods: Consecutive adult PRP subjects were enrolled, along with an equal number of SSc and HC. Peripheral blood perfusion of the hands was assessed by laser speckle contrast analysis (LASCA). PDG was then calculated applying a generalizable formula independent of both intra- and inter-personal factors. Non-specific anti-nuclear autoantibody (ANA) isolated positivity was assessed., Results: Fifty PRP patients (88 % female, mean age 45 ± 17.9 years) were enrolled, along with 50 SSc patients and 50 HC. After adjusting mean PDG results for age and sex, no significant differences emerged between PRP and SSc (1.80 ± 0.43 vs 1.76 ± 0.53; p = 0.294). Conversely, PRP values were significantly reduced when compared to HC (2.72 ± 0.37; p < 0.001). Among PRP subjects, no significant differences were found regarding isolated ANA positivity (1.86 ± 0.44 vs 1.74 ± 0.44; p = 0.42)., Conclusion: PRP and SSc seems to share the same basal PDG perfusion impairment assessed by LASCA. Isolated ANA positivity, in the absence of clinical and capillaroscopic suspicion for secondary causes, should not be considered an exclusion criterion for PRP classification., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Osteoporosis is a prevalent bone disease with a relevant burden of mortality and comorbidity, especially due to fragility fractures occurring as a result of reduced bone mineral density. In this review we provide a critical digest of the most recent literature regarding the relationship between gut microbiota and osteoporosis, and discuss the role of radiofrequency echographic multi-spectrometry (REMS) and machine learning in the diagnostic work-up and prevention of osteoporosis.

Objectives: To evaluate the performance of oropharyngoesophageal scintigraphy (OPES) in the assessment of dysphagia in patients with systemic sclerosis (SSc), and to compare OPES results with those of barium esophagogram., Methods: Adult SSc patients who underwent OPES for the assessment of dysphagia were enrolled. OPES was performed with both liquid and semisolid boluses and provided information regarding oropharyngeal transit time, esophageal transit time (ETT), oropharyngeal retention index (OPRI), esophageal retention index (ERI), and site of bolus retention. Barium esophagogram results were also collected., Results: Fifty-seven SSc patients (87.7% female, mean age 57.7 years) with dysphagia were enrolled. OPES identified at least one alteration in each patient and findings were generally worse for the semisolid bolus. Esophageal motility was widely impaired with 89.5% of patients with an increased semisolid ERI, and middle-lower esophagus was the most frequent site of bolus retention. However, oropharyngeal impairment was highlighted by widespread increased OPRI, especially in anti-topoisomerase I positivity. Older patients and with longer disease duration presented slower semisolid ETT (p = 0.029 and p = 0.002, respectively). Eleven patients with dysphagia had a negative barium esophagogram: all of them presented some alterations in OPES parameters., Conclusion: OPES revealed a marked SSc esophageal impairment, in terms of both slowed transit time and increased bolus retention, but also shed light on oropharyngeal swallowing alterations. OPES showed high sensitivity, being able to detect swallowing alterations in dysphagic patients with negative barium esophagogram. Therefore, the use of OPES for the assessment of SSc-related dysphagia in clinical practice should be promoted., (© 2023. The Author(s).)

Systemic sclerosis (SSc) is an autoimmune disease characterised by microvasculopathy, immune dysregulation, and skin and visceral organ fibrosis. Every year novel insights into the pathogenesis, organ involvement and treatment of this severe disease are published in the scientific community.In this review we report an overview of some of the most relevant contributions published in 2021.

This study aimed to determine COVID-19 recovery time and identify predictors among hospitalized patients in the Dhanusha District of Madhesh Province, Nepal. This hospital-based longitudinal study involved 507 COVID-19 patients admitted to three distinct medical facilities for therapeutic intervention between April and October 2021. Data were collected for patient demography, symptoms, vital signs, oxygen saturation levels, temperatures, heart rates, respiratory rates, blood pressure measurements, and other health-related conditions. Kaplan–Meier survival curves estimated the recovery time, and a Cox proportional hazard model was used to identify the predictors of recovery time. For the total participants, mean age was 51.1 (SD = 14.9) years, 68.0% were males. Of the total patients, 49.5% recovered, and 16.8% died. The median for patient recovery was 26 days (95% CI: 25.1–26.7). Patients with severe or critical conditions were less likely to recover compared to those with milder conditions (hazard ratio (HR) = 0.34, 95% CI: 0.15–0.79; p = 0.012). In addition, an increase in oxygen saturation was associated with an elevated likelihood of recovery (HR = 1.09, 95% CI = 1.01–1.17, p = 0.018). This study underscores the need for early admission to hospital and emphasizes the targeted interventions in severe cases. Additionally, the results highlight the importance of optimizing oxygen levels in COVID-19 patient care. [ABSTRACT FROM AUTHOR]

The increasing burden of type 2 diabetes (T2D), in relation to alarming rise in the prevalence; challenges in the diagnosis, prevention, and treatment; as well as the substantial impact of disease on longevity and quality of life, is a major concern in healthcare worldwide. Sulfonylureas (SUs) have been a cornerstone of T2D pharmacotherapy for over 60 years as oral antidiabetic drugs (OADs), while the newer generation SUs, such as gliclazide modified release (MR), are known to be associated with low risk of hypoglycemia in addition to the cardiovascular neutrality. This scoping review aimed to specifically address the current position of gliclazide MR among other SUs in the contemporary treatment paradigm for T2D and to provide a practical guidance document to assist clinicians in using gliclazide MR in real-life clinical practice. The main topics addressed in this paper include the role of early and sustained glycemic control and use of SUs in T2D management, the properties of gliclazide MR in relation to its effectiveness and safety, the use of gliclazide therapy in special populations, and the place of SUs as a class and gliclazide MR specifically in the current T2D treatment algorithm. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the impact of reductions in various body mass components on the erythrocyte oxidative status and glycemic state of people with obesity (PWO). Methods: A total of 53 PWO followed a six-month individualized low-calorie diet with exercise, during which anthropometric, biochemical, and oxidative parameters were measured. The participants were divided into groups based on weight (W), visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses, as well as normoglycemia (NG) and hyperglycemia (HG). Results: Weight reduction normalized glycemia and influenced erythrocyte enzyme activity. Regardless of the tissue type lost (VFA, TBW, or SMM), glutathione peroxidase activity decreased in all groups, accompanied by an increase in glutathione reductase activity. Lipofuscin (LPS) and malondialdehyde (MDA) concentrations decreased regardless of the type of tissue lost. The α-/γ-tocopherol ratio increased in those losing >10% body weight, >15% VFA, and >5% TBW. In the NG group, compared to the HG group, there was a decrease in glutathione peroxidase and an increase in glutathione reductase, with these changes being stronger in the HG group. The LPS and MDA concentrations decreased in both groups. Significant correlations were observed between glucose reduction and changes in catalase, retinol, and α-tocopherol, as well as between VFA reduction and changes in vitamin E, L-LPS, and the activities of L-GR and L-GST. Conclusions: This analysis highlights the complex interactions between glucose metabolism, oxidative state, and erythrocyte membrane integrity, crucial for understanding diabetes and its management. This study shows the significant metabolic adaptability of erythrocytes in response to systemic changes induced by obesity and hyperglycemia, suggesting potential therapeutic targets to improve metabolic health in obese individuals. [ABSTRACT FROM AUTHOR]

The transcriptional regulator nuclear factor-κB (NF-κB) is a mediator of endothelial dysfunction. Inhibiting NF-κB with salsalate is used to investigate inflammatory mechanisms contributing to accelerated cardiovascular disease risk. However, in the absence of disease, inhibition of NF-κB can impact redox mechanisms, resulting in paradoxically decreased endothelial function. This study aimed to measure microvascular endothelial function during inhibition of the transcriptional regulator NF-κB in reproductive-aged healthy women. In a randomized, single-blind, crossover, placebo-controlled design, nine healthy women were randomly assigned oral salsalate (1,500 mg, twice daily) or placebo treatments for 5 days. Subjects underwent graded perfusion with the endothelium-dependent agonist acetylcholine (ACh, 10−10 to 10−1 M, 33°C) alone and in combination with 15 mM NG-nitro- l -arginine methyl ester [ l -NAME; nonselective nitric oxide (NO) synthase inhibitor] through intradermal microdialysis. Laser-Doppler flux was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated as flux divided by mean arterial pressure and normalized to site-specific maximum (CVC%max; 28 mM sodium nitroprusside + 43°C). The l -NAME sensitive component was calculated as the difference between the areas under the dose-response curves. During the placebo and salsalate treatments, the l -NAME sites were reduced compared with the control sites (both P < 0.0001). Across treatments, there was a significant difference between the control and l -NAME sites, where both sites shifted upward following salsalate treatment (both P < 0.0001), whereas the l -NAME-sensitive component was not different (P = 0.94). These data demonstrate that inhibition of the transcriptional regulator NF-κB improves cutaneous microvascular function in reproductive-aged healthy women through non-NO-dependent mechanisms. NEW & NOTEWORTHY: The transcription factor nuclear factor-κB (NF-κB) regulates multiple aspects of innate and adaptive immunity by encoding for genes that participate in inflammation and impact endothelial function following NF-κB inhibition with salsalate treatment. Our results show that cutaneous microvascular function is increased through non-nitric oxide (NO)-dependent mechanisms following salsalate treatment in reproductive-aged healthy women. [ABSTRACT FROM AUTHOR]

Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes and muscle weakness. Here the authors show that statin-treated female mice show reduced levels of docosahexaenoic acid (DHA) and that the adverse effects are prevented by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene. [ABSTRACT FROM AUTHOR]

The intrarenal endothelin (ET) system is an established moderator of kidney physiology and mechanistic contributor to the pathophysiology and progression of chronic kidney disease in humans and rodents. The aim of the present study was to characterize ET system by combining single cell RNA sequencing (scRNA-seq) data with immunolocalization in human and rodent kidneys of both sexes. Using publicly available scRNA-seq data, we assessed sex and kidney disease status (human), age and sex (rats), and diurnal expression (mice) on the kidney ET system expression. In normal human biopsies of both sexes and in rodent kidney samples, the endothelin-converting enzyme-1 (ECE1) and ET-1 were prominent in the glomeruli and endothelium. These data agreed with the scRNA-seq data from these three species, with ECE1/Ece1 mRNA enriched in the endothelium. However, the EDN1/Edn1 gene (encodes ET-1)was rarely detected, even though it was immunolocalized within the kidneys, and plasma and urinary ET-1 excretion are easily measured. Within each species, there were some sex-specific differences. For example, in kidney biopsies from living donors, men had a greater glomerular endothelial cell endothelin receptor B (Ednrb) compared with women. In mice, females had greater kidney endothelial cell Ednrb than male mice. As commercially available antibodies did not work in all species, and RNA expression did not always correlate with protein levels, multiple approaches should be considered to maintain required rigor and reproducibility of the pre- and clinical studies evaluating the intrarenal ET system. [ABSTRACT FROM AUTHOR]

Among numerous public health actions, the Prevention Departments of Local Health Authorities take charge of the migrant asylum-seeking population for health assessments, for the implementation of preventive activities, and for any consequent actions. This report describes two cases of tuberculosis in Belluno Province managed by a multidisciplinary team made up of healthcare workers that involved numerous diagnostic, clinical, and prophylactic implications, as well as an analysis of the epidemiological aspects related to the incidence of cases along the migration route. Although the cases occurred in a northeastern Italian territory, the management methods described here may represent good practices to share on this operational line, which can promote the strengthening of cooperation between Health Authorities and Emergency Reception Centers to correctly identify cases of active tuberculosis that may not have been initially screen-detected. [ABSTRACT FROM AUTHOR]

Evidence suggests that insulin resistance plays an important role in developing diabetes complications. The association between insulin resistance and pain perception is less well understood. This study aimed to investigate the effects of peripheral insulin deficiency on pain pathways in the brain. Diabetes was induced in 60 male rats with streptozotocin (STZ). Insulin was injected into the left ventricle of the brain by intracerebroventricular (ICV) injection, then pain was induced by subcutaneous injection of 2.5% formalin. Samples were collected at 4 weeks after STZ injection. Dopamine (DA), serotonin, reactive oxygen species (ROS), and mitochondrial glutathione (mGSH) were measured by ELISA, and gene factors were assessed by RT‐qPCR. In diabetic rats, the levels of DA, serotonin, and mGSH decreased in the nuclei of the thalamus, raphe magnus, and periaqueductal gray, and the levels of ROS increased. In addition, the levels of expression of the neuron‐specific enolase and receptor for advanced glycation end genes increased, but the expression of glial fibrillary acidic protein expression was reduced. These results support the findings that insulin has an analgesic effect in non‐diabetic rats, as demonstrated by the formalin test. ICV injection of insulin reduces pain sensation, but this was not observed in diabetic rats, which may be due to cell damage ameliorated by insulin. [ABSTRACT FROM AUTHOR]

Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent β-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet β-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent β-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated β-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated β-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced β-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of β-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH. [ABSTRACT FROM AUTHOR]

Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements. It has been suggested that autophagy promotes β-cell survival by delaying apoptosis and providing adaptive responses to mitigate the detrimental effects of ER stress and DNA damage, which is directly related to oxidative stress. As people with diabetes are now living longer, they are more susceptible to a different set of complications. There has been a diversification in causes of death, whereby a larger proportion of deaths among individuals with diabetes is attributable to nonvascular conditions; on the other hand, the proportion of cancer-related deaths has remained stable or even increased in some countries. Due to the increasing cases of both T1D and T2D, these diseases become even more socially significant. Hence, we believe that search for any opportunities for control of this disease is an overwhelmingly important target for the modern science. We focus on two differences that are characteristic of the development of diabetes’s last periods. One of them shows that all-cause death rates have declined in several diabetes populations, driven in part by large declines in vascular disease mortality but large increases in oncological diseases. Another hypothesis is that some T2D medications could be repurposed to control glycemia in patients with T1D. [ABSTRACT FROM AUTHOR]

Simple Summary: This article reviews the biological importance of the Thioredoxin-1 system in different cells and organs. Redox balance, defined by an equilibrium between oxidized and reduced molecules, is crucial for proper cellular functions in health. Disruption of this balance may lead to cell death. Oxidation and reduction of cysteine residues in key signaling molecules changes their structural conformation and function. Thioredoxin-1 is a key regulatory protein that is used as a buffer to maintain the proteins in their optimal shape. In this review, we specifically focus on transgenic animal models related to the Thioredoxin-1 system. This review aims to showcase the specific roles of the Thioredoxin-1 system in maintaining balance in various organs and cell types. Redox balance is increasingly identified as a major player in cellular signaling. A fundamentally simple reaction of oxidation and reduction of cysteine residues in cellular proteins is the central concept in this complex regulatory mode of protein function. Oxidation of key cysteine residues occurs at the physiological levels of reactive oxygen species (ROS), but they are reduced by a supply of thiol antioxidant molecules including glutathione, glutaredoxin, and thioredoxin. While these molecules show complex compensatory roles in experimental conditions, transgenic animal models provide a comprehensive picture to pinpoint the role of each antioxidant. In this review, we have specifically focused on the available literature on thioredoxin-1 system transgenic models that include thioredoxin and thioredoxin reductase proteins. As the identification of thioredoxin protein targets is technically challenging, the true contribution of this system in maintaining cellular balance remains unidentified, including the role of this system in the brain. [ABSTRACT FROM AUTHOR]

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Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae. Besides, it may cause alterations in primary, secondary, and tertiary hemostasis. Importantly, these responses have been highly decisive in the evolution of infected patients also diagnosed with diabetes mellitus (DM), who showed previous endothelial dysfunction. In this review, we provide an overview of the potential triggers of endothelial activation related to COVID-19 and COVID-19 under diabetic milieu. Several mechanisms are induced by both the viral particle itself and by the subsequent immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, activation of the complement system). Alterations in coagulation mediators such as factor VIII, fibrin, tissue factor, the von Willebrand factor: ADAMST-13 ratio, and the kallikrein-kinin or plasminogen-plasmin systems have been reported. Moreover, an imbalance of thrombotic and thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation and hypofibrinolysis. In the context of DM, these mechanisms can be exacerbated leading to higher loss of hemostasis. However, a series of therapeutic strategies targeting the activated endothelium such as specific antibodies or inhibitors against thrombin, key cytokines, factor X, complement system, the kallikrein-kinin system or NETosis, might represent new opportunities to address this hypercoagulable state present in COVID-19 and DM. Antidiabetics may also ameliorate endothelial dysfunction, inflammation, and platelet aggregation. By improving the microvascular pathology in COVID-19 and post-COVID subjects, the associated comorbidities and the risk of mortality could be reduced. [ABSTRACT FROM AUTHOR]

Adverse pregnancy outcomes (APOs: hypertensive disorders, gestational diabetes, preterm birth, and placental disorders) are associated with cardiovascular disease risk or blood volume abnormalities. Traditional risk factors might not identify highest risk people in the early years after APO deliveries. Test the hypothesis that vascular function is worse, and plasma volume-regulating renal hormones are lower after delivery in people who did versus did not have an APO. Adult participants 6 mo-3 years postdelivery of a singleton infant participated in this cross-sectional study. Exclusion criteria included current smoking, current use of certain medications, and diabetes outside of pregnancy. Differences in measurements between participants with versus without APOs were determined with t tests or Wilcoxon tests. Associations of renal hormones with APO history were assessed with linear regression, adjusted for age, race, body mass index (BMI), and sodium consumption. Of 86 participants, 38 (44%) had an APO history. Those with APOs were more likely to identify as Black and had a higher BMI, 34.0 kg/m² [interquartile range (IQR), 24.6, 39.3] versus 24.2 kg/m² [IQR, 21.2, 31.3], P < 0.05. Most brachial and all aortic blood pressures were higher in those with APOs: median aortic blood pressure was 102/74 versus 96/68 mmHg, P = 0.05. There were no differences in arterial stiffness or endothelial function between groups. Aldosterone was lower (54 [IQR, 28-84] vs. 80 [IQR, 39-150] pmol/L) in participants with past APOs. Blood pressures were higher, and aldosterone was lower in participants with past APOs. Associations of aldosterone with APO history persisted after adjustment. Neither renin nor aldosterone were related to vascular function. [ABSTRACT FROM AUTHOR]

Edible oils had made an important contribution to the diet of people in many countries serving as a good source of proteins, lipids, and fatty acids. The purpose of this study is to evaluate the quality of the oils, based on the physicochemical parameters of some vegetable oils. Five edible oils were obtained, of which 2 were imported (avocado oil, palm oil), and 3 of them were domestically produced (olive oil, corn oil, sunflower oil). The samples were taken randomly in local markets in Tirana, Albania. Selection of the representative samples for each type of oil was carried out starting from the products that are widely used by consumers. The quality of these oils was analyzed by determining physicochemical properties such as density, index of refraction, acid value, saponification value, and peroxide value. Classical methods of analysis were used. The palm oil sample has high values of density (0.9152 g/mL) compared to the FAO/WHO standards. This shows that we have the presence of other added oils. Acid value is often used as a general indication of the condition and edibility of the oil. The acid value for all edible oils were below 0.6 mgKOH/g obtained from FAO/WHO recommendation. Olive oil has refractive index values of 1.4685 which is within the standards obtained from FAO/WHO, while the values of other oils are different from the required standards, or: avocado oil - 1.4734, maize oil - 1.4764, sunflower oil - 1.4764, and palm oil -1.4757, respectively. The different value of the refractive index indicates that foreign fats are present. It is noted that maize oil, sunflower oil, and palm oil have a lower number of saponification compared to the FAO/WHO recommendations: maize oil - 177.68 mg KOH/g, sunflower oil - 182.39mg KOH/g, and palm oil - 184.80 mg KOH/g, respectively. The lower saponification value indicates a low triacylglycerol content, consistent with the low ester value, and also indicates that the oil has no potential to be used for the cosmetic industry. We observed that palm oil had the lowest quality according to standards recommendation. [ABSTRACT FROM AUTHOR]

Background: Toxic Heavy Metals (THMs) threaten food safety and result in human poisonings. It seems to be few studies on THMs contamination in food chain in developing countries. Current investigation determine the concentration and health risk of arsenic (As), cadmium (Cd), lead (Pb), as well as mercury (Hg) in fish and water at Nsukka, Metropolis, Enugu state, Nigeria. Methods: Forty eight samples; 24 (catfish and tilapia) fish and 24 (borehole, sachet, and bottled) water were randomly collected from two major markets and districts in Nsukka Metropolis and were evaluated for THMs using Atomic Absorption Spectrophotometer. The Estimated Daily Intake, Target Hazard Quotient, Hazard Index, and Cancer Risk (CR) were assessed as well. Results: THMs analaysis showed that As, Cd, and Hg were at 100% and Pb being at 16% in all the fish samples while 12.5% of fish of exceeded the Hg Maximum Permissible Limit (MPL) of 0.050 mg/kg, that not statistically significant (p>0.05). On the other hand, based on the analysis of all water samples, Hg and As were detected at 100% rate, Cd at 58.3% while Pb was not identified. The values above the MPL appeared to be 9 (37.5%), 2 (8.3%), and 3(12.5%) for Hg, As, and Cd, respectively in water while not statistically significant (p>0.05). The mean value of Hg (0.06425 mg/kg) in roasted fish as well as Cd (0.0065 and 0.0105) mg/ml in tap and bottled water respectively surpassed the MPL although not statistically significant (p>0.05). The Estimated Daily Intake of THMs except Cd in fish were proved to be within the Provisional Tolerable Daily Intake in contrast with As and Cd in water. CR is present both in children and adults with CR value >1. Conclusion: The finding of THMs in fish and water above the MPL is regarded as potential health risk for the consumers of such contaminated water and fish in the investigation scope. [ABSTRACT FROM AUTHOR]

The cultivated olive (Olea europaea L. subsp. europaea var. europaea) is one of the most valuable fruit trees worldwide. However, the hormonal mechanisms underlying the fruit growth and ripening in olives remain largely uncharacterized. In this study, we investigated the physiological and hormonal changes, by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), as well as the expression patterns of hormone-related genes, using quantitative real-time PCR (qRT-PCR) analysis, during fruit growth and ripening in two olive cultivars, 'Arbequina' and 'Picual', with contrasting fruit size and shape as well as fruit ripening duration. Hormonal profiling revealed that olive fruit growth involves a lowering of auxin (IAA), cytokinin (CKs), and jasmonic acid (JA) levels as well as a rise in salicylic acid (SA) levels from the endocarp lignification to the onset of fruit ripening in both cultivars. During olive fruit ripening, both abscisic acid (ABA) and anthocyanin levels rose, while JA levels fell, and SA levels showed no significant changes in either cultivar. By contrast, differential accumulation patterns of gibberellins (GAs) were found between the two cultivars during olive fruit growth and ripening. GA1 was not detected at either stage of fruit development in 'Arbequina', revealing a specific association between the GA1 and 'Picual', the cultivar with large sized, elongated, and fast-ripening fruit. Moreover, ABA may play a central role in regulating olive fruit ripening through transcriptional regulation of key ABA metabolism genes, whereas the IAA, CK, and GA levels and/or responsiveness differ between olive cultivars during olive fruit ripening. Taken together, the results indicate that the relative absence or presence of endogenous GA1 is associated with differences in fruit morphology and size as well as in the ripening duration in olives. Such detailed knowledge may be of help to design new strategies for effective manipulation of olive fruit size as well as ripening duration. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which involves widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. In order to correlate scientific data from the literature with clinical experience, we present the case of a 56-year-old woman who was diagnosed with systemic sclerosis 16 years ago. The association of numerous comorbidities characterized by a considerable level of seriousness characterizes this case: the highly extensive systemic damage, the cardiovascular impact of the illness, and the existence of severe pulmonary arterial hypertension. The systemic and clinical manifestations, respiratory functional tests, radiological features, and specific therapy are discussed. [ABSTRACT FROM AUTHOR]

Background. Adiponectin acts to prevent vascular dysfunction due to obesity by inhibiting ICAM-1 and VCAM-1 expressions. Objective. We investigate adiponectin ICAM-1, VCAM-1, and metabolic syndrome (MetS) in obese adolescents. Methods. A cross-sectional study with healthy obese adolescents aged 13 to 18 years was conducted from October 2019 to January 2020. Statistical analysis conducted was a test of normality and homogeneity tests, ANOVA/Kruskal–Wallis, independent sample T-test/Mann–Whitney U test, and Spearman correlation and determined as significant if p value <0.05. Results. 125 obese adolescents were recruited. 42 (33.6%) were obese with MetS (we grouped as MetS) and 83 (66.4%) subjects without MetS (non-MetS group). VCAM-1 was significantly higher on boys with MetS compared to girls with MetS, and even girls with MetS had lower levels of VCAM-1 than boys with non-MetS. ICAM-1 was significantly higher in boys with low-level HDL-c (p < 0.05) and correlated weakly with HDL-c, while adiponectin levels were significantly lower in girls with central obesity and hypertriglyceridemia. Path analysis showed that triglyceride had a direct effect on ICAM-1 but not VCAM-1 in both obese boys and girls. Adiponectin had a negative direct effect on ICAM-1 and VCAM-1 in girls. However, on boys, diastole blood pressure had a negative direct effect, which might be the role of sex hormones indirectly. Conclusion. VCAM-1 was significantly higher in boys than girls, which showed that boys had a higher risk of atherosclerosis. ICAM-1 showed no significant difference in both gender and metabolic states. Adiponectin showed a protective effect by lowering ICAM-1 and VCAM-1 directly on girls. [ABSTRACT FROM AUTHOR]

Mechanisms underlying vascular endothelial susceptibility to infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are not fully understood. Emerging evidence indicates that patients lacking von Willebrand factor (vWF), an endothelial hallmark, are less severely affected by SARS‐CoV‐2 infection, yet the precise role of endothelial vWF in modulating coronavirus entry into endothelial cells is unknown. In the present study, we demonstrated that effective gene silencing by short interfering RNA (siRNA) for vWF expression in resting human umbilical vein endothelial cells (HUVECs) significantly reduced by 56% the cellular levels of SARS‐CoV‐2 genomic RNA. Similar reduction in intracellular SARS‐CoV‐2 genomic RNA levels was observed in non‐activated HUVECs treated with siRNA targeting angiotensin‐converting enzyme 2 (ACE2), the cellular gateway to coronavirus. By integrating quantitative information from real‐time PCR and high‐resolution confocal imaging, we demonstrated that ACE2 gene expression and its plasma membrane localization in HUVECs were both markedly reduced after treatment with siRNA anti‐vWF or anti‐ACE2. Conversely, siRNA anti‐ACE2 did not reduce endothelial vWF gene expression and protein levels. Finally, SARS‐CoV‐2 infection of viable HUVECs was enhanced by overexpression of vWF, which increased ACE2 levels. Of note, we found a similar increase in interferon‐β mRNA levels following transfection with untargeted, anti‐vWF or anti‐ACE2 siRNA and pcDNA3.1‐WT‐VWF. We envision that siRNA targeting endothelial vWF will protect against productive endothelial infection by SARS‐CoV‐2 through downregulation of ACE2 expression and might serve as a novel tool to induce disease resistance by modulating the regulatory role of vWF on ACE2 expression. [ABSTRACT FROM AUTHOR]

Vascular aging represents a collection of structural and functional changes in a blood vessel with advancing age, including increased stiffness, vascular wall remodeling, loss of angiogenic ability, and endothelium-dependent vasodilation dysfunction. These age-related alterations may occur earlier in those who are at risk for or have cardiovascular diseases, therefore, are defined as early or premature vascular aging. Vascular aging contributes independently to cardio-cerebral vascular diseases (CCVDs). Thus, early diagnosis and interventions targeting vascular aging are of paramount importance in the delay or prevention of CCVDs. Here, we review the direct assessment of vascular aging by examining parameters that reflect changes in structure, function, or their compliance with age including arterial wall thickness and lumen diameter, endothelium-dependent vasodilation, arterial stiffness as well as indirect assessment through pathological studies of biomarkers including endothelial progenitor cell, lymphocytic telomeres, advanced glycation end-products, and C-reactive protein. Further, we evaluate how different types of interventions including lifestyle mediation, such as caloric restriction and salt intake, and treatments for hypertension, diabetes, and hyperlipidemia affect age-related vascular changes. As a single parameter or intervention targets only a certain vascular physiological change, it is recommended to use multiple parameters to evaluate and design intervention approaches accordingly to prevent systemic vascular aging in clinical practices or population-based studies. [ABSTRACT FROM AUTHOR]

Background: Hexavalent chromium (CrVI) is known to be a potentially hepatotoxic and nephrotoxic contaminant in humans and other animals, whose toxicity is associated with oxidative stress and inflammation. The aim of this study was to evaluate the potential protective effect of chlorogenic acid (CGA), which has known anti-inflammatory and antioxidant effects, on potassium dichromate (PDC)-induced acute hepatotoxicity and nephrotoxicity in rats., Methods and Results: Thirty-six Wistar albino rats were treated with CGA (10, 20, or 40 mg/kg, intraperitoneally) and/or PDC (15 mg/kg/day, intraperitoneally) as a single dose. Serum, liver, and kidney tissues were examined biochemically, histopathologically, and immunohistochemically. Compared to the control group, a significant increase in interleukin-6 (IL-6) levels and a significant decrease in serum and renal reduced glutathione (GSH) levels, liver catalase (CAT), tumour necrosis factor-alpha (TNF-α), and interleukin 1β (IL-1β) levels were observed in the PDC group. The administration of PDC led to histopathological and immunohistochemical changes in rat liver and kidney tissues. With the administration of CGA, especially at the 10 mg/kg dosage, the above-mentioned parameters approached normal levels., Conclusions: CGA had antioxidant and anti-inflammatory effects that alleviated PDC-induced acute hepato- and nephrotoxicity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Hexavalent chromium (Cr 6+ ) is one of the stable oxidation states of chromium that has been reported to elicit various toxic effects in aquatic organisms. However, the mechanisms of Cr 6+ toxicity are still poorly understood. Thus, the present study investigated the tissue accumulation, cytotoxic, oxidative stress, and immunotoxic effects of Cr 6+ in juvenile Clarias gariepinus. The fish were exposed to waterborne Cr 6+ concentrations (0, 0.42, 0.84, and 1.68 mg/L) for 28 days, after which they were sacrificed and various organs were harvested for the determination of Cr 6+ levels. Other parameters that were indicators of oxidative stress, cytotoxicity, and immunotoxicity were measured. Cr 6+ accumulated more in the kidney and liver of the exposed fish, especially at the highest concentration. The levels of lipid peroxidation and DNA fragmentation increased significantly in the exposed fish. The activities of superoxide dismutase and lactate dehydrogenase increased significantly in exposed fish compared to the control. The total white blood cells, lymphocytes, and neutrophils counts were significantly higher in the exposed fish compared to the control fish. The respiratory burst activity decreased significantly in the exposed fish while the myeloperoxidase content did not differ significantly. There were upregulations of TNF-α and HSP 70 while CYP II and MHC 2 were downregulated in the exposed fish. Also, exposure to Cr 6+ resulted in various histopathological alterations in the architecture of the head kidney. The results indicate concentration-dependent toxic effects of Cr 6+ in C. gariepinus. The study reveals the potentials of Cr 6+ to accumulate in the different tissues of fish and caused cytotoxic, oxidative stress, and immunotoxic effects in the exposed fish., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study deliberates on the biochemical characterization of a highly alkalophilic and thermostable polygalacturonase (PGase) from Pseudomonas sp. 13,159,349. Further, its efficacy in olive-oil extraction was also assessed. The PGase enzyme was produced using wheat bran solid substrate fermentation (SSF) media that was statistically optimised using Placket-Burman and RSM. The extracellularly secreted PGase was purified by gel permeation chromatography with a fold purification of 6.42 and a specific activity of 192.97 U/mg. 12% SDS-PAGE and LC-MS spectra confirmed that the enzyme has a molecular weight of 44.5 kDa. PGase exhibited optimum activity at pH 9 and 45 − 50 °C and the enzyme retained > 50% stability at alkaline pH 9, 10, as well as 45 and 50 °C even after 8 h. The enzyme's kinetic parameters (Km and Vmax) with pectin substrate were found to be 0.0663 mg/ml and 209.60 mol. min-1, respectively. Metal ions Co2+ and Mn2+ enhanced enzyme activity while Ag2+, Hg2+, and ethylenediaminetetraacetic acid (EDTA) reduced it. Activity could be restored by removing EDTA by dialysis, demonstrating PGase as a metalloenzyme. In addition, the use of non-ionic surfactants displayed considerable stability, while Triton-X 100 increased the activity significantly, indicating a greater interaction between enzyme and substrate. Furthermore, treatment of olive paste with 300 U and 600 U of PGase remarkedly (P < 0.05) increased the olive oil output by 1.96 to 2.35-fold (p < 0.01) in comparison to the control. It also improved the total polyphenol content by 23 and 33% (p < 0.05) respectively. Overall, the biochemical characterization of PGase has provided substantial insights into the enzyme characteristics and revealed its prospective applicability in the oil sector. [ABSTRACT FROM AUTHOR]

This review focuses on the multiple and reciprocal relationships that exist between oxidative stress, hyperglycemia and diabetes and related metabolic disorders. Human metabolism uses most of the consumed glucose under aerobic conditions. Oxygen is needed in the mitochondria to obtain energy, as well as for the action of microsomal oxidases and cytosolic pro-oxidant enzymes. This relentlessly generates a certain amount of reactive oxygen species (ROS). Although ROS are intracellular signals necessary for some physiological processes, their accumulation leads to oxidative stress, hyperglycemia, and progressive resistance to insulin. A cellular pro-oxidant versus an antioxidant equilibrium would regulate ROS levels, but oxidative stress, hyperglycemia, and pro-inflammatory conditions feed back to each other and the relevance of the interconnections tends to increase those conditions. Hyperglycemia promotes collateral glucose metabolism through protein kinase C, polyols and hexosamine routes. In addition, it also facilitates spontaneous glucose auto-oxidation and the formation of advanced glycation end products (AGEs), which in turn interact with their receptors (RAGE). The mentioned processes undermine cellular structures, finally giving place to a progressively greater degree of oxidative stress with further hyperglycemia, metabolic alterations, and diabetes complications. NFκB is the major transcription factor involved in the expression of most of the pro-oxidant mediators, while Nrf2 is the major transcription factor regulating the antioxidant response. FoxO is also involved in the equilibrium, but its role is controversial. This review summarizes the key factors linking the diverse glucose metabolic routes enhanced in hyperglycemia with ROS formation and vice versa, emphasizing the role of the major transcription factors involved in the desirable balance between pro-oxidant and antioxidant proteins. [ABSTRACT FROM AUTHOR]

Introduction: A few studies have explored the association of resting heart rate (RHR) with mortality and/or other oncological outcomes in patients with specific cancers such as breast, colorectal, and lung cancer. This study aimed to evaluate the association between the RHR and oncological outcomes in patients with early-stage cervical cancer (CC) who underwent radical surgical resection. Methods: We included 622 patients with early-stage CC (stages IA2–IB1). The patients were divided into four groups based on the RHR as follows: quartile 1, ≤64; quartile 2, 65–70; quartile 3, 71–76; and quartile 4, >76 beats per min (bpm), with the lowest quartile being the reference group. We evaluated the associations of the RHR and clinicopathological features with oncological outcomes using Cox proportional-hazards regression. Results: There were clear among-group differences. Further, there was a significant positive correlation of RHR with tumor size and deep stromal invasion. Multivariate analysis revealed that RHR was an independent prognostic factor for disease-free survival (DFS) and overall survival (OS). Compared with patients with an RHR ≤70 bpm, those with an RHR of 71–76 bpm had a 1.84- and 3.05-times higher likelihood of DFS (p = 0.016) and OS (p = 0.030), respectively, while those with RHR >76 bpm had a 2.20-times higher likelihood of DFS (p = 0.016). Conclusion: This is the first study to demonstrate that RHR may be an independent prognostic factor for oncological outcomes in patients with CC. [ABSTRACT FROM AUTHOR]

As a toxic metal, hexavalent chromium (CrVI) has effects on both the reproductive and endocrine systems. This study aimed to evaluate the protective effects of selenium (Se) and zinc (Zn) against the toxicity of chromium on the placenta in pregnant Wistar albino rats. Thirty pregnant Wistar rats were divided into control and four treated groups, receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10 mg/kg body weight (bw)) alone, or in association with Se (0.3 mg/kg bw), ZnCl2 (20 mg/kg bw), or both of them simultaneously. Plasma steroid hormones, placenta histoarchitecture, oxidative stress profile, and developmental parameters were investigated. These results showed that K2Cr2O7 exposure induced a significant increase in the levels of both plasma estradiol (E2) and placenta malondialdehyde (MDA), the number of fetal resorptions, and percent of post-implantation loss. On the other hand, K2Cr2O7 significantly reduced developmental parameters, maternal body and placenta weight, and plasma progesterone (P) and chorionic gonadotropin hormone (β HCG) levels. However, K2Cr2O7 significantly decreased the placenta activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and nonprotein sulfhydryl (NPSH). These changes have been reinforced by histopathological evaluation of the placenta. Se and/or ZnCl2 supplementation provoked a significant improvement in most indices. These results suggest that the co-treatment with Se or ZnCl2 strongly opposes the placenta cytotoxicity induced by K2Cr2O7 through its antioxidant action. [ABSTRACT FROM AUTHOR]

This study was aimed to describe the most frequently recorded disorders in dogs in Alexandria Government and provides a prevalence baseline against which to measure progress in canine health. The surgical conditions affecting the eyes, mouth and nose and its surrounding structures are numerous. These conditions affect adversely the general health condition of the animal as it is causing disruption of the important biological processes in the body. In the present study, a total number of 422 pet animals suffering from different surgical conditions were recorded. The surgical conditions of the eye and its surrounding structures represented about 25.11% of the encountered surgical conditions along this study with maximum incidence of diseases of nictating membrane. Meanwhile, the surgical conditions of the mouth and their surrounding structures were recorded in 14.21% of the encountered surgical conditions. The surgical conditions of the nose represent 0.47 %. The results of the present study revealed that the surgical conditions affecting the eyes and its related structures were recorded in 106 cases. These conditions include eyelid laceration and trauma (17 cases), eye lid abscess (1 case), eye lid neoplasia (2 cases), entropion (10 cases), neonatal defect in eyelid opening (5 cases), eye proptosis (2 cases), eye infection (1 case) and diseases of nictating membrane (68 cases). The mouth and nose disorders include dental tartar (13 cases), periodontal diseases (3 cases), persisting deciduous teeth and polydontium (3 cases), neoplastic lesion (3 cases), foreign body in mouth (22 cases), lip wound (16 cases), and epistaxis (2 cases). Most of the surgical disorders of the mouth and related structures affected the animal's health and are usually associated with difficult mastication. These disorders usually required immediate surgical interferences. German Shepherd, Rottweiler and Pit bull recorded highest incidence of disorders with maximum cases in young age group up to 2 years 104 cases (24.63%) of age. Sex wise incidence was higher in male 101 cases (23.91%) dogs. [ABSTRACT FROM AUTHOR]

With healthcare costs rising, many affected by ailments are turning to alternative medicine for treatment. More people are choosing to complement their pharmacological regimen with dietary supplements from natural products. In this study, the compound composition of Kalanchoe Pinnata (K. pinnata) and the effects of combined preparations of K. pinnata and metformin on antioxidant activity in human skeletal muscle myoblasts (HSMMs) and human diabetic skeletal muscle myoblasts (DHSMMs) were investigated. Ultraperformance liquid chromatography fusion orbitrap mass spectrometry (UPLC-OT-FTMS) identified biologically active flavanols in K. pinnata. The main compounds identified in locally grown K. pinnata were quercetin, kaempferol, apigenin, epigallocatechin gallate (EGCG), and avicularin. Antioxidant results indicated that a combinatorial preparation of K. pinnata with metformin may modulate antioxidant responses by increasing the enzymatic activity of superoxide dismutase and increasing levels of reduced glutathione. A combination of 50 μM and 150 μg/mL of metformin and K. pinnata, respectively, resulted in a significant increase in reduced glutathione levels in non-diabetic and diabetic human skeletal muscle myoblasts and H2O2-stress-induced human skeletal muscle myoblasts. Additionally, a K. pinnata treatment (400 µg/mL) alone significantly increased catalase (CAT) activity for non-diabetic and diabetic human skeletal muscle myoblasts and a H2O2-stress-induced human skeletal muscle myoblast cell line, while significantly lowering malondialdehyde (MDA) levels. However, the treatment options were more effective at promoting cell viability after 24 h versus 72 h and did not promote cell viability after 72 h in H2O2-stress-induced HSMM cells. These treatment options show promise for treating oxidative-stress-mediated pathophysiological complications associated with type II diabetes. [ABSTRACT FROM AUTHOR]

Reduced glutathione (GSH) is the most abundant non-protein endogenous thiol. It is a ubiquitous molecule produced in most organs, but its synthesis is predominantly in the liver, the tissue in charge of storing and distributing it. GSH is involved in the detoxification of free radicals, peroxides and xenobiotics (drugs, pollutants, carcinogens, etc.), protects biological membranes from lipid peroxidation, and is an important regulator of cell homeostasis, since it participates in signaling redox, regulation of the synthesis and degradation of proteins (S-glutathionylation), signal transduction, various apoptotic processes, gene expression, cell proliferation, DNA and RNA synthesis, etc. GSH transport is a vital step in cellular homeostasis supported by the liver through providing extrahepatic organs (such as the kidney, lung, intestine, and brain, among others) with the said antioxidant. The wide range of functions within the cell in which glutathione is involved shows that glutathione's role in cellular homeostasis goes beyond being a simple antioxidant agent; therefore, the importance of this tripeptide needs to be reassessed from a broader metabolic perspective. [ABSTRACT FROM AUTHOR]

Arachidonic acid (AA) is a key precursor for proinflammatory and anti-inflammatory derivatives that regulate the inflammatory response. The modulation of AA metabolism is a target for searching a therapeutic agent with potent anti-inflammatory action in cardiovascular disorders. Therefore, our study aims to determine the potential preventive impact of N-acetylcysteine (NAC) supplementation on myocardial inflammation and the occurrence of oxidative stress in obesity induced by high-fat feeding. The experiment was conducted for eight weeks on male Wistar rats fed a standard chow or a high-fat diet (HFD) with intragastric NAC supplementation. The Gas-Liquid Chromatography (GLC) method was used to quantify the plasma and myocardial AA levels in the selected lipid fraction. The expression of proteins included in the inflammation pathway was measured by the Western blot technique. The concentrations of arachidonic acid derivatives, cytokines and chemokines, and oxidative stress parameters were determined by the ELISA, colorimetric, and multiplex immunoassay kits. We established that in the left ventricle tissue NAC reduced AA concentration, especially in the phospholipid fraction. NAC administration ameliorated the COX-2 and 5-LOX expression, leading to a decrease in the PGE2 and LTC4 contents, respectively, and augmented the 12/15-LOX expression, increasing the LXA4 content. In obese rats, NAC ameliorated NF-κB expression, inhibiting the secretion of proinflammatory cytokines. NAC also affected the antioxidant levels in HFD rats through an increase in GSH and CAT contents with a simultaneous decrease in the levels of 4-HNE and MDA. We concluded that NAC treatment weakens the NF-κB signaling pathway, limiting the development of myocardial low-grade inflammation, and increasing the antioxidant content that may protect against the development of oxidative stress in rats with obesity induced by an HFD. [ABSTRACT FROM AUTHOR]

Antibodies against the SARS-CoV-2 nucleocapsid protein are produced by the immune system in response to SARS-CoV-2 infection, but most available vaccines developed to fight the pandemic spread target the SARS-CoV-2 spike protein. The aim of this study was to improve the detection of antibodies against the SARS-CoV-2 nucleocapsid by providing a simple and robust method applicable to a large population. For this purpose, we developed a DELFIA immunoassay on dried blood spots (DBSs) by converting a commercially available IVD ELISA assay. A total of forty-seven paired plasma and dried blood spots were collected from vaccinated and/or previously SARS-CoV-2-infected subjects. The DBS-DELFIA resulted in a wider dynamic range and higher sensitivity for detecting antibodies against the SARS-CoV-2 nucleocapsid. Moreover, the DBS-DELFIA showed a good total intra-assay coefficient of variability of 14.6%. Finally, a strong correlation was found between SARS-CoV-2 nucleocapsid antibodies detected by the DBS-DELFIA and ELISA immunoassays (r = 0.9). Therefore, the association of dried blood sampling with DELFIA technology may provide an easier, minimally invasive, and accurate measurement of SARS-CoV-2 nucleocapsid antibodies in previously SARS-CoV-2-infected subjects. In conclusion, these results justify further research to develop a certified IVD DBS-DELFIA assay for detecting SARS-CoV-2 nucleocapsid antibodies useful for diagnostics as well as for serosurveillance studies. [ABSTRACT FROM AUTHOR]