Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle.

Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes viral pneumonia through cytokine storms and systemic inflammation. Cellular autophagy pathways play a role in coronavirus replication and inflammation. The Silent Information Regulator 1 (SIRT1) pathway, linked to autophagy, protects cells via FOXO3, inhibits apoptosis, and modulates SIRT1 in type-II epithelial cells. SIRT1 activation by adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) enhances the autophagy cascade. This pathway holds therapeutic potential for alveolar and pulmonary diseases and is crucial in lung inflammation. Angiotensin-converting enzyme 2 (ACE-2) activation, inhibited by reduced expression, prevents COVID-19 virus entry into type-II epithelial cells. The coronavirus disease 2019 (COVID-19) virus binds ACE-2 to enter into the host cells, and XBB.1.5 COVID-19 displays high ACE-2-binding affinity. ACE-2 expression in pneumocytes is regulated by signal transducers and activators of transcription-3 (STAT3), which can increase COVID-19 virus replication. SIRT1 regulates STAT3, and the SIRT1/STAT3 pathway is involved in lung diseases. Therapeutic regulation of SIRT1 protects the lungs from inflammation caused by viral-mediated oxidative stress. Scopoletin, as a modulator of the SIRT1 cascade, can regulate autophagy and inhibit the entry and life cycle of XBB.1.5 COVID-19 in host cells.

Understanding the Role of Galectin-1 in Heart Failure: A Comprehensive Narrative Review.

Heart failure (HF) is the fastest-growing cardiovascular condition worldwide. The immune system may play a role in the development of HF since this condition is associated with elevated pro-inflammatory cytokine levels. HF is a life-threatening disease, and there is an increasing demand for diagnostic biomarkers, prognostic factors, and therapeutic agents that can help treat it. Galectin-1 (Gal-1) is the prototype galectin of the lectin family. Multiple signal transduction pathways are regulated by Ras proteins, which act as a molecular switch in cells. Gal-1 regulates T and B cell activation, differentiation, and survival. Gal-1 has been linked to inflammation. Activated T cells produce Gal-1 through an autocrine apoptotic mechanism involving MEK1/ERK and p38 MAPK. In the cardiovascular system, atherosclerosis is facilitated by Gal-1. Heart disease, myocardial infarction, hypertension, and stroke can be caused by atherosclerotic plaque. HF and heart hypertrophy are caused by decreased cardiac L-type Ca2+ channel activity. Deregulation of Gal-1 and CaV1.2 in pathological cardiac hypertrophy suggests a possible target for anti-hypertrophic therapy. Rat hypertrophic cardiomyocytes express Gal-1 and CaV1.2 channels simultaneously. It has been reported that diastolic dysfunction (DD) is associated with elevated Gal-1 levels. The high Gal-1 level in subjects led to the lowest cumulative survival as a composite endpoint. Incidences of HF, DD, and serum Gal-1 levels correlated significantly. The ejection fraction was negatively correlated with Gal-1 and CRP concentrations. Based on two different approaches in mice and humans, Gal-1 was identified as a potential mediator of HF.

Scutellarin alleviates lipopolysaccharide-provoked septic nephrotoxicity via attenuation of inflammatory and oxidative events and mitochondrial dysfunction.

BACKGROUND: Sepsis-associated acute kidney injury (AKI) is highlighted by high incidence of mortality and morbidity. Scutellarin is a flavone extracted from certain medicinal plants with anti-inflammatory and anti-oxidative properties. This research study was done to investigate the beneficial effect of scutellarin on lipopolysaccharide (LPS) murine model of AKI. MATERIALS AND METHODS: Five groups of mice were used including control (without LPS injection), LPS group (LPS injection, 10 mg/kg), and LPS + Scutellarin25, 50, and/or 100 groups (receiving scutellarin orally at different doses of 25, 50, or 100 mg/kg before LPS injection). RESULTS: Scutellarin pretreatment effectively lowered kidney function markers (BUN, creatinine, and cystatin C), improved superoxide dismutase (SOD) besides enhancement of level, and/or gene expression for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) and also reduced oxidative stress factors including reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, scutellarin reduced tissue level and/or gene expression of inflammatory markers comprising toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB), and tumor necrosis factor α (TNF-α) and properly raised anti-inflammatory factor IL-10. Moreover, scutellarin enhanced mitochondrial membrane potential (MMP) and attenuated histopathological changes in renal tissue subsequent to LPS challenge. Beneficial effects of scutellarin was associated with improvement of gene expression regarding peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PGC-1α as specific markers of mitochondrial biogenesis. CONCLUSION: These results indicate that scutellarin could protect against LPS-provoked AKI through restraining inflammation and oxidative stress and maintenance of mitochondrial health and biogenesis which is partly mediated through its regulation of Nrf2/PPAR-γ/PGC-1α/NF-kB/TLR4.

A systematic review on COVID-19 vaccination and cosmetic filler reactions: A focus on case studies and original articles.

BACKGROUND: Tissue fillers are among the most popular cosmetic procedures performed and notably, cases of filler reactions after COVID-19 vaccination have been reported. OBJECTIVE: The objective was to determine the characteristics of patients with filler reaction after COVID-19 vaccination and address several considerations that have to be taken into practice. METHODS: A PRISMA compliant systematic search was conducted in Scopus, Web of Science, and PubMed/MEDLINE databases for articles published from inception up to October 21, 2021. RESULTS: Out of 106 initially retrieved articles, four of them were included in our study, and a total number of 13 cases were analyzed. In this study, we found that all of the patients who developed delayed-type reaction (DTR) following COVID-19 vaccination were middle-aged women without any known history of allergy to foods or drugs. All patients had a history of hyaluronic acid (HA) filler injection in their head and neck and demonstrated symptoms particularly swelling, from <1 day up to 10 days after the first or second doses of vaccines. Lisinopril, hyaluronidase, and corticosteroids seemed to have good results in management. CONCLUSION: Although rare, DTR to fillers after COVID-19 vaccination can happen. Physicians should be aware of the pathogenesis and management of this phenomenon.

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2.

Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.

Mucocutaneous manifestations of patients with chronic kidney disease under hemodialysis: A cross-sectional study of 49 patients.

Chronic kidney disease (CKD) is a common medical problem with well-known dermatologic manifestations, some of which highly disturb the patients' quality of life. This cross-sectional study was designed to identify the prevalence and type of cutaneous involvement in CKD patients. The skin manifestations of 49 patients with CKD undergoing hemodialysis at Akhavan Hospital in Kashan, Iran, were recorded over 2 months. Diabetes (35%) was the most common cause of chronic renal failure in the patients, and the most common skin manifestations were xerosis (95.9%), uremic pigmentation (89.8%), scleral discoloration (87.8%), dental discoloration (85.2% among the patients with natural teeth), dry mouth (65.3%), varicosity (61.2%), pruritus (57.1%), skin atrophy (49%), lentigo (46.9%), subungual hyperkeratosis (42.9%), half and half nail dystrophy (34.7%), and purpura (26.5%). Mucocutaneous involvement has a very high prevalence in CKD patients undergoing hemodialysis, and some of the cases are medically and cosmetically disturbing; therefore, with better knowledge about the type and prevalence of these involvements, the consequences can be better predicted and managed. Further studies are recommended to be conducted on the association between these signs and CKD grade, and clinical trials are also required for establishing the treatment options available for these signs and then assessing the patients' quality of life as a primary outcome measure.

S-allyl cysteine, an active ingredient of garlic, attenuates acute liver dysfunction induced by lipopolysaccharide/ d-galactosamine in mouse: Underlying mechanisms.

In the present study, beneficial effect of S-allyl cysteine (SAC) was evaluated in the lipopolysaccharide/d-galactosamine (LPS/d-Gal) model of acute liver injury (ALI). To mimic ALI, LPS and d-Gal (50 µg/kg and 400 mg/kg, respectively) were intraperitoneally administered and animals received SAC per os (25 or 100 mg/kg/d) for 3 days till 1 hour before LPS/d-Gal injection. Pretreatment of LPS/d-Gal group with SAC-lowered activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and partially reversed inappropriate alterations of hepatic oxidative stress- and inflammation-related biomarkers including liver reactive oxygen species, malondialdehyde, and hepatic activity of the defensive enzyme superoxide dismutase, ferric reducing antioxidant power (FRAP), toll-like receptor-4 (TLR4), cyclooxygenase 2, NLR family pyrin domain containing 3 (NLRP3), caspase 1, nuclear factor κB (NF-κB), interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor-α, and myeloperoxidase activity. Additionally, SAC was capable to ameliorate apoptotic biomarkers including caspase 3 and DNA fragmentation. In summary, SAC can protect liver against LPS/d-Gal by attenuation of neutrophil infiltration, oxidative stress, inflammation, apoptosis, and pyroptosis which is partly linked to its suppression of TLR4/NF-κB/NLRP3 signaling.

Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress, inflammation, and apoptosis.

CONTEXT: Acute kidney injury (AKI) is considered a major public health concern in today's world. Sepsis-induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram-negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects. OBJECTIVE: In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI. METHODS: LPS was injected at a single dose of 10 mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100 mg/kg, one hour prior to LPS. RESULTS: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS. CONCLUSION: In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.

Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects.

Systemic inflammation during infectious disorders usually accompanies chronic complications including cognitive dysfunction. Neuroinflammation and cognitive deficit are also observed in some debilitating neurological disorders like Alzheimer's and Parkinson's diseases. Genistein is a soy isoflavone with multiple beneficial effects including anti-inflammatory, anti-oxidative, and protective properties. In this research study, the effect of genistein in prevention of lipopolysaccharide (LPS)-induced cognitive dysfunction was investigated. LPS was given i.p. (500 µg/kg/day) and genistein was orally given (10, 50, or 100 mg/kg) for one week. Findings showed that genistein could dose-dependently attenuate spatial recognition, discrimination, and memory deficits. Additionally, genistein treatment of LPS-challenged group lowered hippocampal level of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) and catalase and glutathione (GSH) level. Furthermore, genistein ameliorated hippocampal acetylcholinesterase (AChE) activity in LPS-challenged rats. Furthermore, genistein administration to LPS-injected group lowered hippocampal level of interleukin 6 (IL-6), nuclear factor-kappaB (NF-κB) p65, toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP), and increased hippocampal level of antioxidant element nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In conclusion, genistein alleviated LPS-induced cognitive dysfunctions and neural inflammation attenuation of oxidative stress and AChE activity and appropriate modulation of Nrf2/NF-κB/IL-6/TNFα/COX2/iNOS/TLR4/GFAP.