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: Concurrent chemoradiotherapy (CCRT)-induced oral mucositis (OM) causes oral pain, malnutrition, and impaired quality of life in patients with head and neck cancer (HNC). Phytochemicals play a potential role in eliminating cancer therapy toxicity.
UNASSIGNED: To evaluate the effect of phytochemical-rich vegetable and fruit juice (VFJ) consumption in preventing CCRT-induced OM among patients with locally advanced HNC.
UNASSIGNED: Forty-nine patients with HNC undergoing CCRT were enrolled. All patients received nutritional counseling before CCRT and weekly follow-up. The VFJ group (25 patients) received 600 mL/day VFJ, 5 days/week for two weeks preceding CCRT and during CCRT, and the control group (24 patients) did not. The contents of total polyphenols and carotenoids in the VFJ were determined. Changes in anthropometric, dietary, and laboratory profiles were compared. Assessment of OM was based on the World Health Organization (WHO) scoring system.
UNASSIGNED: Total polyphenols content was 64.6 mg gallic acid equivalents per 100 mL of the VFJ, and the main carotenoids were β-carotene and lycopene. The mean daily consumption of the VFJ was 538 mL for VFJ group. Changes in body weight, albumin, and energy intake were not significantly different between the two groups. The incidence of ulcerative OM was significantly lower in VFJ (64.0%) than in control (95.8%) subjects at week 6 of CCRT. Multiple logistic regressions revealed that VFJ consumption correlated significantly with lower risks of ulcerative OM.
UNASSIGNED: Consumption of VFJ rich in phytochemicals including total polyphenols and carotenoids effectively alleviates the severity of CCRT-induced OM among patients with locally advanced HNC.
UNASSIGNED: Preventive Medicine; Dietary Therapy/Nutrition Supplements.
UNASSIGNED: (classification by EVISE)Preventive medicine, dietary therapy, nutrition supplements.

UNASSIGNED: To evaluate trends in the use of epidural analgesia and nonopioid and opioid analgesics for patients undergoing lobectomy from 2009 to 2018.
UNASSIGNED: We queried the Premier database for adult patients undergoing open, video-assisted, and robotic-assisted lobectomy from 2009 to 2018. The outcome of interest was changes in the receipt of epidural analgesia and nonopioid and opioid analgesics as measured by charges on the day of surgery. We also evaluated postoperative daily opioid use. We used multivariable logistic and linear regression models to examine the association between the utilization of each analgesic modality and year.
UNASSIGNED: We identified 86,308 patients undergoing lobectomy from 2009 to 2018 within the Premier database: 35,818 (41.5%) patients had open lobectomy, 35,951 (41.7%) patients had video-assisted lobectomy, and 14,539 (16.8%) patients had robotic-assisted lobectomy. For all 3 surgical cohorts, epidural analgesia use decreased, and nonopioid analgesics use increased over time, except for intravenous nonsteroidal anti-inflammatory drugs. Use of patient-controlled analgesia decreased, while opioid consumption on the day of surgery increased and postoperative opioid consumption did not decrease over time.
UNASSIGNED: In this large sample of patients undergoing lobectomy, utilization of epidural analgesia declined and use of nonopioid analgesics increased. Despite these changes, opioid consumption on day of surgery increased, and there was no significant reduction in postoperative opioid consumption. Further research is warranted to examine the association of these changes with patient outcomes.

Cardiovascular diseases are a major cause of mortality, and vascular injury, a common pathological basis of cardiovascular disease, is deeply correlated with macrophage apoptosis and inflammatory response. Genistein, a type of phytoestrogen, exerts cardiovascular protective activities, but the underlying mechanism has not been fully elucidated. In this study, RAW264.7 cells were treated with genistein, lipopolysaccharide (LPS), nuclear factor-kappa B (NF-κB) inhibitor, and/or protein kinase B (AKT) agonist to determine the role of genistein in apoptosis and inflammation in LPS-stimulated cells. Simultaneously, high fat diet-fed C57BL/6 mice were administered genistein to evaluate the function of genistein on LPS-induced cardiovascular injury mouse model. Here, we demonstrated that LPS obviously increased apoptosis resistance and inflammatory response of macrophages by promoting miR-21 expression, and miR-21 downregulated tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) expression by targeting the coding region. Genistein reduced miR-21 expression by inhibiting NF-κB, then blocked toll-like receptor 4 (TLR4) pathway and AKT phosphorylation dependent on TIPE2, resulting in inhibition of LPS. Our research suggests that miR-21/TIPE2 pathway is involved in M1 macrophage apoptosis and inflammatory response, and genistein inhibits the progression of LPS-induced cardiovascular injury at the epigenetic level via regulating the promoter region of Vmp1 by NF-κB.

BACKGROUND: Uncontrolled inflammation causes health problems. Extracellular signal-regulated kinase (ERK) phosphorylates signal transducer and activator of transcription 3 (STAT3) at Ser727, resulting in inflammation. The leaf of Vernonia amygdalina (VA) is a medicinal herb for managing inflammation-associated diseases. Oral administration or topical application of VA leaf extract exerts anti-inflammatory effects in rat models. However, the anti-inflammatory mechanisms of the herb are not fully understood.
OBJECTIVE: In this study, we aimed to investigate the involvement of ERK/STAT3 (Ser727) signaling in the anti-inflammatory effects of an ethanolic extract of VA leaves.
METHODS: Extracts of VA leaves were prepared with different concentrations of ethanol. A LPS-stimulated RAW264.7 cell model was used for in vitro assays, and a TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model was employed for in vivo assays. The 95% ethanol extract of VA leaves (VAE) exerted the strongest inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages; thus it was selected for use in this study. Hematoxylin and eosin (H&E) staining was used to examine pathological conditions of mouse ear tissues. Griess reagent was employed to examine NO generation in cell cultures. Immunoblotting and ELISA were used to examine protein levels, and RT-qPCR was employed to examine mRNA levels.
RESULTS: Topical application of VAE ameliorated mouse ear edema induced by TPA. VAE suppressed the phosphorylation of ERK (Thr202/Tyr204) and STAT3 (Ser727); and decreased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in the mouse ear tissues and in LPS-stimulated RAW 264.7 cells. VAE also inhibited NO production, and lowered mRNA levels of IL-6, IL-1β and TNF-α in the macrophages.
CONCLUSIONS: VAE ameliorates TPA-induced mouse ear edema. Suppression of ERK/STAT3 (Ser727) signaling is involved in VAE\'s anti-inflammatory effects. These novel data provide further pharmacological justifications for the medicinal use of VA in treating inflammation-associated diseases, and lay the groundwork for developing VAE into a new anti-inflammatory agent.

Moringa oleifera Lam. (M. oleifera Lam) is a perennial tropical deciduous tree that belongs to the Moringaceae family. Polysaccharides are one of the major bioactive compounds in M. oleifera Lam and show immunomodulatory, anticancer, antioxidant, intestinal health protection and antidiabetic activities. At present, the structure and functional activities of M. oleifera Lam polysaccharides (MOPs) have been widespread, but the research data are relatively scattered. Moreover, the relationship between the structure and biological activities of MOPs has not been summarized. In this review, the current research on the extraction, purification, structural characteristics and biological activities of polysaccharides from different sources of M. oleifera Lam were summarized, and the structural characteristics of purified polysaccharides were focused on this review. Meanwhile, the biological activities of MOPs were introduced, and some molecular mechanisms were listed. In addition, the relationship between the structure and biological activities of MOPs was discussed. Furthermore, new perspectives and some future research of M. oleifera Lam polysaccharides were proposed in this review.

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

UNASSIGNED: Several recent studies have stated that glycyrrhizin and licorice extract are present in most traditional Chinese medicine formulas used against SARS-CoV-2 in China. Significant data are showing that glycyrrhizin and licorice extract have multiple beneficial activities in combating most features of SARS-CoV-2.
UNASSIGNED: The aim of current review was to highlight recent progresses in research that showed the evidence of the potential use of glycyrrhizin and licorice extract against COVID-19.
UNASSIGNED: We have reviewed the information published from 1979 to October 2020. These studies demonstrated the effects , use and safety of glycyrrhizin and icorice extract against viral infections,bacterial infections, inflammatory disorders of lung ( in vitro and in vivo).  These studies were collated through online electronic databases research (Academic libraries as PubMed, Scopus, Web of Science and Egyptian Knowledge Bank).
UNASSIGNED: Pooled effect size of articles provides information about the rationale for using glycyrrhizin and licorice extract to treat COVID-19. Fifty studies demonstrate antiviral activity of glycyrrhizin and licorice extract. The most frequent mechanism of the antiviral activity is due to disrupting viral uptake into the host cells and disrupting the interaction between receptor- binding domain (RBD) of SARS-COV2 and ACE2 in recent articles. Fifty studies indicate that glycyrrhizin and licorice extract have significant antioxidant, anti-inflammatory and immunomodulatory effects. Twenty five studies provide evidence for the protective effect of glycyrrhizin and licorice extract against inflammation-induced acute lung injury and cardiovascular disorders.
UNASSIGNED: The current study showed several evidence regarding the beneficial effects of glycyrrhizin and licorice extract in combating COVID-19. More randomized clinical trials are needed to obtain a precise conclusion.

This research investigated the reno-protective effect of Thunbergia laurifolia Linn. (TL) in a lead-induced toxicity test through the modulation of cell signaling pathways. The study carried out to evaluate the effect of TL leaf extracts in Swiss Albino mice exposed to lead acetate (PbAc). Prior to in vivo study, a probable kidney-protective effect of the plant leaf extract was presumed through an activity-specific (PASS) molecular docking analysis. In animal model study, albino mice were divided in seven groups and co-treated with PbAc and TL (100, 200 mg/kgBW) or vitamin E (100 mg/kgBW) for 38 days, whereas the untreated control, TL control, and vehicle control groups received sodium acetate, PbAc, sodium acetate plus mineral oil, respectively. At the end of treatment, blood and kidney tissue were collected for investigating Pb concentration, estimating biochemical profile, evaluating oxidative stress and inflammatory parameters. The histopathological change of kidney along with apoptosis was assessed from kidney sections using H & E staining and TUNEL assay. Pb-exposed mice were found to be increased concentration of Pb in the blood and kidney sample, which further led to increased MDA levels in the plasma, blood, and tissue. Followed by kidney damage, increased expression of TNF-α, iNOS, and COX-2 in kidney tissues were noticed, which were related to elevated TNF-α in the systemic circulation of Pb-treated mice. Co-treatment with TL or vitamin E significantly reduced altered structure and apoptosis of kidney tissues. Downregulation of inflammatory markers especially TNF-α, iNOS, and COX-2 with simultaneous improvement of renal function through reduced plasma BUN and creatinine levels demonstrate that TL act as a potential dietary supplement to detoxify Pb in kidney showing an antioxidant and anti-inflammatory effect.

Diazinon (DZN) with prominent neurotoxic effects perturbs CNS function via multiple mechanisms. This investigation intends to explore mood, spatial learning, and memory dysfunction, acetylcholine esterase (AChE) activity, and neurodegeneration-related gene expression in the cortex and hippocampus regions of mice exposed to DZN for 63 consecutive days (subchronic exposure). Adult male albino mice were orally given sublethal DZN (DZNL = 0.1 mg/kg, DZNM = 1 mg/kg and DZNH = 10 mg/kg). All mice in the DZNH group died within 3 weeks postexposure. DZNL and DZNM caused body and brain weight loss (p < 0.05). Completing 9 weeks of DZN exposure, a marked decline in AChE activity and oxidative stress level was indicated in both brain regions (p < 0.05). Also, synaptophysin, vesicular acetylcholine transferase, and glutamate decarboxylase gene expressions were affected in both brain regions (p < 0.05). Furthermore, the present study revealed that DZN administration increased anxiety and depressive-like behaviors (p < 0.0001). Spatial learning and short- and long-memory were severely affected by DZNL and DZNM treatments (p < 0.0001). Taken together, subchronic exposure to low and medium doses of DZN can cause AChE inhibition, oxidative damage, and neurotransmitter disturbances in brain cells and induce neurodegeneration. These changes would impair mood, spatial learning, and memory function.