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With the increasing lifespan of human, cardiovascular diseases (CVDs) and cancer are the main diseases leading to the death in the world. Aging is related to a progressive decline in cardiovascular function and structure. While human body suffer from oxidative stress, reactive oxygen species (ROS) are generated as metabolic by-products, which lead to inactivate proteins, damage nucleic acids, and alter the fatty acids of lipids. The accumulation of this oxidative damage contributes to the development of heart disease, diabetes, chronic inflammatory diseases, and cancer. Polyphenols have been widely studied as an anti-oxidant agent in the world. Danshen, the dried root or rhizome of Salvia miltiorrhiza Bunge. is a common Traditional Chinese medicine used in cardiovascular disease and cancer. The main polyphenols in Danshen are phenolic acids (including Salvianolic acids A and B, rosmarinic acid, and their derivatives) and flavonoids. Salvianolic acids have potent anti-oxidative capabilities due to their polyphenolic structure and exhibit cardiovascular protection through mechanisms of ROS scavengers, reduction of leukocyte-endothelial adherence, inhibition of inflammation and indirect regulation of immune function. Salvianolic acids A and B have been reported to owe anti-cancer, anti-inflammatory activities not only through inducing apoptosis, halting cell cycle and adjourning metastasis by targeting multiple deregulated signaling networks of cancer but also sensitizing cancer cells to chemotherapeutic agents.

IL-18 is emerging as an IL-22-induced and epithelium-derived cytokine which contributes to host defence against intestinal infection and inflammation. In contrast to its known role in Goblet cells, regulation of barrier function at the molecular level by IL-18 is much less explored. Here we show that IL-18 is a bona fide IL-22-regulated gate keeper for intestinal epithelial barrier. IL-22 promotes crypt immunity both via induction of phospho-Stat3 binding to theIl-18gene promoter and viaIl-18independent mechanisms. In organoid culture, while IL-22 primarily increases organoid size and inhibits expression of stem cell genes, IL-18 preferentially promotes organoid budding and induces signature genes of Lgr5+stem cells via Akt-Tcf4 signalling. During adherent-invasiveE. coli(AIEC) infection, systemic administration of IL-18 corrects compromised T-cell IFNγ production and restores Lysozyme+Paneth cells inIl-22−/−mice, but IL-22 administration fails to restore these parameters inIl-18−/−mice, thereby placing IL-22-Stat3 signalling upstream of the IL-18-mediated barrier defence function. IL-18 in return regulates Stat3-mediated anti-microbial response in Paneth cells, Akt-Tcf4-triggered expansion of Lgr5+stem cells to facilitate tissue repair, and AIEC clearance by promoting IFNγ+T cells.

Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn175 of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis., Galectins are carbohydrate binding proteins previously implicated in sensing and repairing damaged lysosomes. Here, the authors show that galectin-9 has specific lysosomal roles in autophagy and contributes to cell degeneration and apoptosis in colitis and pancreatitis in mice.

Background: Dry eye is a common ophthalmologic disorder that causes ocular discomfort and has become a worldwide health concern. Patients with dry eye often turn to complementary and alternative medicine (CAM) because of unsatisfactory conventional treatments. Acupuncture is one of the most popular interventions of CAM used, and laser acupuncture (LA) is a noninvasive technique. Methods: This protocol is a 2-center randomized controlled trial investigating the effect of laser acupuncture on dry eye. Two hundred participants aged 20 to 65 years will be randomly assigned to the experimental group (LA plus conventional treatment) or the sham control group (LA without laser output plus conventional treatment) at 2 clinical research centers in South Taiwan. The subjects will undergo LA treatment thrice a week for 12 weeks. The subjects in the experimental group will sequentially receive 0.375 J of energy at each of the following acupoints: BL2, TE23, ST2, LI4, ST36, and GB37. The subjects in the control group will also receive a sham LA treatment, without any laser output. Outcome assessments will include evaluation of the ocular surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer-I test finding, and the visual analog scale (VAS) score at 4 and 12 weeks before treatment. The OSDI, TFBUT, Schirmer-I test result, and VAS score of the participants will be analyzed and compared between the experimental and control groups using the paired t test and one-way analysis of variance. Objectives: The aim of this protocol is to investigate the efficacy of LA therapy in patients with dry eye. Trial registration: ClinicalTrials.gov NCT03204903.

Rationale: Displaced olecranon fracture is a common injury following a fall or direct trauma to the elbow. There have been no reports of patients with a displaced olecranon fracture who have only received nonoperative manipulative reduction with Chinese herbs. Patient concerns: The patient was a 64-year-old woman with a complex elbow injury that occurred in a traffic accident. The patient complained of severe, painful limitation of motion on straightening or bending. Diagnoses: The patient was diagnosed with a displaced fracture of the left olecranon (type IIA olecranon fracture according to the Mayo classification system). Interventions: The patient underwent nonoperative manipulation with Chinese herbs. Outcomes: The fracture was successfully reduced. After 3 to 4 months of follow-up, severe pain and disability in the elbow were improved following reduction of the left olecranon fracture in which there was no longer a displacement. Lessons: Nonoperative manipulative reduction performed by a well-trained physician with Chinese herbs may be a treatment option for displaced olecranon fractures.

Good nutrition could maintain health and life. Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs. They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide. In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation. The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects. Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress. Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity. Despite the numerous in vivo and in vitro studies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

Aging-associated cardiovascular diseases (CVDs) have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM) has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs.