The efficacy of herbal medicines on the length of stay and negative conversion time/rate outcomes in patients with COVID-19: a systematic review.

Introduction: In recent years, diverse initiatives have been carried out to control the COVID-19 pandemic, ranging from measures restricting social activities to analyzing drugs and vaccines. Studies on herbal medicines are also increasingly conducted in various countries as an adjuvant therapy or supplement. Therefore, this systematic review aimed to investigate the efficacy of herbal medicines analyzed from various countries through clinical trials with the randomized controlled trial method. The outcomes of Length of Stay (LOS), Negative Conversion Time (NCT), and Negative Conversion Rate (NCR) were the main focus. Methods: An extensive review of literature spanning from 2019 to 2023 was carried out using well-known databases including PubMed, Scopus, and Cochrane. The search included relevant keywords such as "randomized controlled trial," "COVID-19," and "herbal medicine." Results: A total of 8 articles were part of the inclusion criteria with outcomes of LOS, NCT, and NCR. In terms of LOS outcomes, all types of herbal medicines showed significant results, such as Persian Medicine Herbal (PM Herbal), Persian Barley Water (PBW), Jingyin Granules (JY granules), Reduning Injection, and Phyllanthus emblica (Amla). However, only JY granules showed significant results in NCR outcome, while JY granules and Reduning Injection showed significant results in reducing NCT. Conclusion: These findings enrich our understanding of the potential benefits of herbal medicines in influencing LOS, NCR and NCT parameters in COVID-19 patients. Herbal medicines worked to treat COVID-19 through antiviral, anti-inflammatory, and immunomodulatory mechanisms.

The Important Role of Phosphatidylserine, ADAM17, TNF-Alpha, and Soluble MER on Efferocytosis Activity in Central Obesity.

Background: Obesity is expected to hinder efferocytosis due to ADAM17-mediated cleavage of the MER tyrosine kinase receptor, producing soluble MER (sMER) that disrupts MERTK binding to cell death markers. However, the intracellular efferocytosis pathway in central obesity remains elusive, particularly the role of low-grade chronic inflammation in its initiation and identification of binding signals that disrupt efferocytosis. Objective: We investigate the efferocytosis signaling pathway in men with central obesity and its relationship with inflammation, cell death, and related processes. Methods: A cross-sectional study was conducted, and clinical data and blood samples were collected from 56 men with central obesity (obese group) and 29 nonobese individuals (control group). Clinical evaluations and predefined biochemical screening tests were performed. The efferocytosis signaling pathway was investigated by measuring phosphatidylserine (PS), ADAM17, TNF-alpha (TNF-α), and sMER. Results: Metabolic syndrome was detected in more than half of the participants in the obese group according to the predefined tests. Mean levels of PS, TNF-α, and sMER were higher in the obese group but not significantly different from those of the control group. Further analysis based on waist circumference (WC) ranges in the obese group revealed a significant increase in PS and sMER levels between the control group and the obese group with WC greater than 120 cm. ADAM17 levels were significantly higher in the obese group than in the control group. PS was positively correlated with WC and ADAM17. ADAM17 was positively correlated with TNF-α and sMER, indicating impaired efferocytosis. Conclusions: Central obesity appeared to cause a disturbance in efferocytosis that began with cell damage and death, along with an enlargement of the WC and an ongoing inflammatory response. Efferocytosis was disrupted by proinflammatory cytokine regulators, which induced the production of sMER and interfered with the efferocytosis process.

V-ATPase subunit C 1 and IKBIP as tandem prospective biomarkers for diabetic nephropathy.

AIMS: The appearance of low-molecular-weight (LMW) protein in the urine indicates any disruption in the structural integrity of the glomerular capillary wall; therefore, the presence of LMW protein may be a potential predictive marker for DN. METHODS: The urine proteomic profiling of T2DM patients (n = 94) and control group (n = 32) was compared by liquid chromatography-tandem mass spectrometry, and the untargeted LMW protein was identified by Progenesis Q1 For Proteomics v4.2. RESULTS: A total of 73 LMW proteins were identified and quantified, of which, 32 proteins were found to be altered significantly (p < 0.05). Further analysis with heat maps identified two potential proteins with the highest folding alterations in urine. V-ATPase subunit C 1 abundance was significantly inversely correlated with microalbumin and significantly decreased in urine, whereas increased IKBIP was positively correlated with microalbumin. The level of those proteins was significantly different among the control, T2DM, and DN groups, implying an association with the progression of DN. CONCLUSIONS: The present findings of our study indicate that the decreasing V-ATPase subunit C 1 together with increasing IKBIP in urine, were found to be closely associated with DN complications and signifying their value as biomarkers for predicting the risk of DN at initial diagnosis.

Update of cellular responses to the efferocytosis of necroptosis and pyroptosis.

Cell death is a basic physiological process that occurs in all living organisms. A few key players in these mechanisms, as well as various forms of cell death programming, have been identified. Apoptotic cell phagocytosis, also known as apoptotic cell clearance, is a well-established process regulated by a number of molecular components, including 'find-me', 'eat-me' and engulfment signals. Efferocytosis, or the rapid phagocytic clearance of cell death, is a critical mechanism for tissue homeostasis. Despite having similar mechanism to phagocytic clearance of infections, efferocytosis differs from phagocytosis in that it induces a tissue-healing response and is immunologically inert. However, as field of cell death has rapid expanded, much attention has recently been drawn to the efferocytosis of additional necrotic-like cell types, such as necroptosis and pyroptosis. Unlike apoptosis, this method of cell suicide allows the release of immunogenic cellular material and causes inflammation. Regardless of the cause of cell death, the clearance of dead cells is a necessary function to avoid uncontrolled synthesis of pro-inflammatory molecules and inflammatory disorder. We compare and contrast apoptosis, necroptosis and pyroptosis, as well as the various molecular mechanisms of efferocytosis in each type of cell death, and investigate how these may have functional effects on different intracellular organelles and signalling networks. Understanding how efferocytic cells react to necroptotic and pyroptotic cell uptake can help us understand how to modulate these cell death processes for therapeutic purposes.

Potential of Quinine Sulfate for COVID-19 Treatment and Its Safety Profile: Review.

The coronavirus disease 2019 (COVID-19) pandemic is currently the largest and most serious health crisis in the world. There is no definitive treatment for COVID-19. Vaccine administration has begun in various countries, but no vaccine is 100% effective. Some people are not protected after vaccination, and there are some groups of people who cannot be vaccinated therefore, research on COVID-19 treatment still needs to be done. Of the several drugs under study, chloroquine (CQ) and hydroxychloroquine (HCQ) are quite controversial, although they have good activity against SARS-CoV-2, both drugs have serious side effects. Indonesia with its wealth of natural ingredients has one potential compound, quinine sulfate (QS), which has the same structure and activity as CQ and HCQ and a better safety profile. The aim of this article was to review the potential of QS against the SARS-Cov-2 virus and outline its safety profile. We conclude that QS has the potential to be developed as a COVID-19 treatment with a better safety profile than that of CQ and HCQ.

Genomics, Proteomics and Metabolomics Approaches for Predicting Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients.

BACKGROUND: There is a continuous rise in the prevalence of type 2 diabetes mellitus (T2DM) worldwide and most patients are unaware of the presence of this chronic disease at the early stages. T2DM is associated with complications related to long-term damage and failure of multiple organ systems caused by vascular changes associated with glycated end products, oxidative stress, mild inflammation, and neovascularization. Among the most frequent complications of T2DM observed in about 20-40% of T2DM patients is diabetes nephropathy (DN). METHODS: A literature search was made in view of highlighting the novel applications of genomics, proteomics and metabolomics, as the new prospective strategy for predicting DN in T2DM patients. RESULTS: The complexity of DN requires a comprehensive and unbiased approach to investigate the main causes of disease and identify the most important mechanisms underlying its development. With the help of evolving throughput technology, rapidly evolving information can now be applied to clinical practice. DISCUSSION: DN is also the leading cause of end-stage renal disease and comorbidity independent of T2DM. In terms of the comorbidity level, DN has many phenotypes; therefore, timely diagnosis is required to prevent these complications. Currently, urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) are gold standards for assessing glomerular damage and changes in renal function. However, GFR estimation based on creatinine is limited to hyperfiltration status; therefore, this makes albuminuria and eGFR indicators less reliable for early-stage diagnosis of DN. CONCLUSION: The combination of genomics, proteomics, and metabolomics assays as suitable biological systems can provide new and deeper insights into the pathogenesis of diabetes, as well as discover prospects for developing suitable and targeted interventions.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary Cross-Sectional Study.

PURPOSE: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. METHODS: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. RESULTS: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. CONCLUSION: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity.

BACKGROUND AND AIM: Previous evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity. METHODS: Plasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n=78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group. RESULTS: In the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r=0.390, P<0.05) and with fatty acid binding protein-4 (FABP4) (r=0.474, P<0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r=-467, P<0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r=0.413, P<0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r=-0.429, P<0.05). CONCLUSIONS: These results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.