Melatonin is the main neuroendocrine product in the pineal gland. Melatonin can regulate circadian rhythm-related physiological processes. Evidence indicates an important role of melatonin in hair follicles, skin, and gut. There appears to be a close association between melatonin and skin disorders. In this review, we focus on the latest research of the biochemical activities of melatonin (especially in the skin) and its promising clinical applications.

UNASSIGNED: Lipopolysaccharides (LPS) stimulate production of inflammatory cytokines. Chrysin is flavonoid beneficial for treatment of inflammatory conditions. Bone marrow mesenchymal stem cell (BM-MSC) exosomes have regenerative ability in different tissues.
UNASSIGNED: To assess potential role of chrysin and BM-MSC exosomes on ultra-structure, viability and function of human dermal fibroblasts-adult (HDFa) stimulated by LPS.
UNASSIGNED: HDFa cells were divided into: Group I: Cells received no treatment. Group II: Cells were stimulated with LPS. Group III: LPS stimulated cells were treated with chrysin. Group IV: LPS stimulated cells were treated with exosomes.
UNASSIGNED: After 48 h, ultrastructural examination of HDFa cells in Group I revealed intact plasma membrane and numerous cytoplasmic organelles. Group II displayed destructed plasma membrane and apoptotic bodies. Group III showed intact plasma membrane with loss of its integrity at some areas. Group IV demonstrated intact plasma membrane that showed fusion with exosomes at some areas. Statistical analysis of MTT represented highest mean value of cell viability% in Group IV followed by Groups III, I and II respectively. Statistical analysis of enzyme-linked immunosorbent assay (ELISA) showed the highest mean value of interleukin-1β (IL-1β) was in Group II followed by Groups III, IV and I, while highest mean values of interleukin-10 (IL-10), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins were in Group I, followed by Groups IV, III and II respectively.
UNASSIGNED: LPS have harmful consequences on ultra-structure, viability and function of HDFa cells. BM-MSC exosomes have better regenerative action on inflamed fibroblasts in comparison to chrysin.

Megalin receptor-mediated endocytosis participates a crucial role in gentamicin (GM) uptake, accumulation, and toxicity. In this study, we investigated the potential effects of montelukast (MLK) on megalin expression/endocytic function against GM nephrotoxicity. Male Wistar rats were administered GM (120 mg/kg; i.p.) daily in divided doses along 4 hr; 30 mg/kg/hr; for 7 days. MLK (30 mg/kg/day) was orally administered 7 days before and then concurrently with GM. The protein expressions of megalin and chloride channel-5 (ClC-5); one of the essential regulators of megalin endocytic function; were determined by Western blotting. Besides, the endocytic function of megalin was evaluated by the uptake of bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) into proximal tubular epithelial cells. Moreover, kidney function biomarkers (Cr, BUN, GFR, KIM-1, cystatin-C) and apoptosis markers (p-AKT1, cleaved caspase-3) were estimated. Co-treatment with MLK downregulated ClC-5 expression leading to reduced recycling of megalin to the plasma membrane, reduced expression, and so impaired endocytic function that was evidenced by reduced uptake of FITC-BSA in proximal tubular epithelial cells. The protein expression of the apoptotic executioner cleaved caspase-3 was significantly reduced, while that of the antiapoptotic p-AKT1 was elevated. These results were confirmed by the improvement of kidney functions and histological findings. Our data suggest that MLK could interfere with megalin expression/endocytic function that could be attributed to downregulation of ClC-5 protein expression. That eventually reduces renal cell apoptosis and improves kidney functions after GM administration without affecting the antibacterial activity of GM. Therefore, reduced expression of ClC-5 and interference with megalin expression/endocytic function by MLK could be an effective strategy against GM nephrotoxicity.

Alzheimer\'s disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found.
Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents.
In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms.
Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aβ) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways.Conclusions.Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD.

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively. Sirt6 knockdown in AML12 cells aggravated APAP-induced hepatocyte death and oxidative stress, inhibited cell viability and proliferation, and downregulated CCNA1, CCND1 and CKD4 protein levels. Sirt6 knockdown significantly prevented APAP-induced NRF2 activation, reduced the transcriptional activities of GSTμ and NQO1 and the mRNA levels of Nrf2, Ho-1, Gstα and Gstμ. Furthermore, SIRT6 showed potential protein interaction with NRF2 as evidenced by co-immunoprecipitation (Co-IP) assay. Additionally, the protective effect of P53 against APAP-induced hepatocytes injury was Sirt6-dependent. The Sirt6 mRNA was significantly down-regulated in P53 -/- mice. P53 activated the transcriptional activity of SIRT6 and exerted interaction with SIRT6. Our results demonstrate that SIRT6 protects against APAP hepatotoxicity through alleviating oxidative stress and promoting hepatocyte proliferation, and provide new insights in the function of SIRT6 as a crucial docking molecule linking P53 and NRF2.

UNASSIGNED: Korean ginseng (Panax ginseng Meyer) contains a variety of ginsenosides that can be metabolized to a biologically active substance, compound K. Previous research showed that compound K could be enriched in the red ginseng extract (RGE) after hydrolysis by pectinase. The current study investigated whether the enzymatically hydrolyzed red ginseng extract (HRGE) containing a notable level of compound K has cognitive improving and neuroprotective effects.
UNASSIGNED: A scopolamine-induced hypomnesic mouse model was subjected to behavioral tasks, such as the Y-maze, passive avoidance, and the Morris water maze tests. After sacrificing the mice, the brains were collected, histologically examined (hematoxylin and eosin staining), and the expressions of antioxidant proteins analyzed by western blot.
UNASSIGNED: Behavioral assessment indicated that the oral administration of HRGE at a dosage of 300 mg/kg body weight reversed scopolamine-induced learning and memory deficits. Histological examination demonstrated that the hippocampal damage observed in scopolamine-treated mouse brains was reduced by HRGE administration. In addition, HRGE administration increased the expression of nuclear-factor-E2-related factor 2 and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase and heme oxygenase-1 in hippocampal tissue homogenates. An in vitro assay using HT22 mouse hippocampal neuronal cells demonstrated that HRGE treatment attenuated glutamate-induced cytotoxicity by decreasing the intracellular levels of reactive oxygen species.
UNASSIGNED: These findings suggest that HRGE administration can effectively alleviate hippocampus-mediated cognitive impairment, possibly through cytoprotective mechanisms, preventing oxidative-stress-induced neuronal cell death via the upregulation of phase 2 antioxidant molecules.