Withanolides: Promising candidates for cancer therapy.

Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.

Targeting TRPs in autophagy regulation and human diseases.

Transient receptor potential channels (TRPs) are widely recognized as a group of ion channels involved in various sensory perceptions, such as temperature, taste, pressure, and vision. While macroautophagy (hereafter referred to as autophagy) is primarily regulated by core machinery, the ion exchange mediated by TRPs between intracellular and extracellular compartments, as well as within organelles and the cytoplasm, plays a crucial role in autophagy regulation as an important signaling transduction mechanism. Moreover, certain TRPs can directly interact with autophagy regulatory proteins to participate in autophagy regulation. In this article, we provide an in-depth review of the current understanding of the regulatory mechanisms of autophagy, with a specific focus on TRPs. Furthermore, we highlight the potential prospects for drug development targeting TRPs in autophagy for the treatment of human diseases.

Zebrafish live imaging: a strong weapon in anticancer drug discovery and development.

Developing anticancer drugs is a complex and time-consuming process. The inability of current laboratory models to reflect important aspects of the tumor in vivo limits anticancer medication research. Zebrafish is a rapid, semi-automated in vivo screening platform that enables the use of non-invasive imaging methods to monitor morphology, survival, developmental status, response to drugs, locomotion, or other behaviors. Zebrafish models are widely used in drug discovery and development for anticancer drugs, especially in conjunction with live imaging techniques. Herein, we concentrated on the use of zebrafish live imaging in anticancer therapeutic research, including drug screening, efficacy assessment, toxicity assessment, and mechanism studies. Zebrafish live imaging techniques have been used in numerous studies, but this is the first time that these techniques have been comprehensively summarized and compared side by side. Finally, we discuss the hypothesis of Zebrafish Composite Model, which may provide future directions for zebrafish imaging in the field of cancer research.

Targeting SERCA2 in Anti-Tumor Drug Discovery.

SERCA2, a P-type ATPase located on the endoplasmic reticulum of cells, plays an important role in maintaining calcium balance within cells by transporting calcium from the cytoplasm to the endoplasmic reticulum against its concentration gradient. A multitude of studies have demonstrated that the expression of SERCA2 is abnormal in a wide variety of tumor cells. Consequently, research exploring compounds that target SERCA2 may offer a promising avenue for the development of novel anti-tumor drugs. This review has summarized the anti-tumor compounds targeting SERCA2, including thapsigargin, dihydroartemisinin, curcumin, galangin, etc. These compounds interact with SERCA2 on the endoplasmic reticulum membrane, disrupting intracellular calcium ion homeostasis, leading to tumor cell apoptosis, autophagy and cell cycle arrest, ultimately producing anti-tumor effects. Additionally, several potential research directions for compounds targeting SERCA2 as clinical anti-cancer drugs have been proposed in the review. In summary, SERCA2 is a promising anti-tumor target for drug discovery and development.

The effect and mechanism of motor imagery based on action observation treatment on dysphagia in Wallenberg Syndrome: a randomized controlled trial.

BACKGROUND: The effect of motor imagery applied to dysphagia patients with Wallenberg syndrome has not yet been reported. AIM: This trial aimed to investigate the effect and mechanism of motor imagery based on action observation treatment in the rehabilitation of patients with dysphagia in Wallenberg syndrome. DESIGN: A randomized controlled trial. SETTING: The setting was in-patient. POPULATION: Thirty patients with dysphagia of Wallenberg syndrome. METHODS: The patients were divided into the experimental group and the control group. Both groups received conventional dysphagia treatment, and the experimental group underwent the addition of motor imagery based on action observation treatment to the control group once a day for 14 days. Overall swallowing function was assessed with specific scales before and after intervention. Meanwhile, the functional near infrared spectroscopy was used to detect changes in cerebral hemodynamics during the execution of volitional swallowing task and swallowing motor imagery. RESULTS: The standardized swallowing assessment score (P=0.030), Murray secretion scale score (P=0.044) and swallowing quality of life score (P=0.011) of the experimental group improved better than those of the control group. In addition, multiple brain regions of the cortical presented extensive activation (P<0.05) during the execution of swallowing motor imagery. Moreover, there were significant differences (P<0.05) in brain regions pre-motor and supplementary motor cortex, right primary motor cortex, and right primary somatosensory cortex of the experimental group before and after treatment. CONCLUSIONS: The present study indicated that motor imagery based on action observation treatment could improve swallowing function for patients with dysphagia of Wallenberg syndrome as an add-on training. As a top-down rehabilitation training, the mechanism of this therapy may be related to the selective activation of mirror neuron system. CLINICAL REHABILITATION IMPACT: Motor imagery based on action observation treatment can be implemented as part of the therapeutic for dysphagia of Wallenberg syndrome.

Enrichment culture combined with microbial electrochemical enhanced low-temperature anaerobic digestion of cow dung.

Enrichment culture combined with the microbial electrochemical system was used to co-enhance the low-temperature (20 °C) anaerobic digestion. The results showed that enrichment culture combined with microbial electrochemical system increased the cumulative methane production in low-temperature anaerobic digestion system by 39.64 % and 133.29 % compared to single and no enrichment culture, respectively. Enrichment culture combined with microbial electrochemical system increased the relative abundance of methanogenic archaea (Methanomassiliicoccus, Methanocorpusculum, unclassified Methanomicrobiaceae, Methanobacterium, Methanoculleus, Methanocalculus) and the relative abundance of cold-tolerant hydrolytic acidifying bacteria (unclassified Bacteroidetes, Treponema). The expressions of specific enzyme genes in the methanogenesis pathway were enhanced, including acetyl-CoA synthetase, formylmethanofuran dehydrogenase, methanol cobalamin methyltransferase, etc. These results indicated that enrichment culture combined with microbial electrochemical system enhanced low-temperature anaerobic digestion methanogenesis by altering microbial communities and stimulating enzyme gene expression to affect volatile fatty acids, pH, redox potential, and reducing sugar parameters.

A novel fuzzy dominant goal programming for portfolio selection with systematic risk and non-systematic risk.

In this paper, we consider a fuzzy portfolio selection problem with systematic risk and non-systematic risk simultaneously. These two kinds of risks are measured by beta coefficient and random error variance obtained by Sharp Single Index Model. The total risk as the objective of portfolio decision is obtained by weighting the two kinds of risk. Among them, the weight of systematic risk λ is regarded as the degree of investors' attention to system risk in economic sense. In addition, the fuzzy return and the degree of diversification are measured by triangular fuzzy number and entropy, respectively. And they are also considered the goal of investment decisions. Hence, a tri-objective portfolio is proposed in this paper. For the fuzzy objectives in the model, a goal programming method based on fuzzy dominance is proposed, which can help investors better capture the ideal point of fuzzy returns according to their risk preference. Finally, combined with the systematic impact of COVID-19 on the financial market, we make an empirical analysis based on our proposed model. The results show that the total risk will be on the high side when λ value is too large or too small. That means paying too much or little attention to the systematic risk will lead investors to bear more risk. In addition, when investors ignore the systematic risk; that is, the λ value is low, and investors will concentrate their funds in the same industry.

Oxidation triggered formation of polydopamine-modified carboxymethyl cellulose hydrogel for anti-recurrence of tumor.

In this research, a hydrogel that combined the tumor photodynamic therapy (PDT) and photothermal therapy (PTT) ability was designed, using dopamine-modified sodium carboxymethyl cellulose (CMC-DA) as the matrix and Chlorin e6 (Ce6) as the photosensitizer. The gel formation was initiated by adding the oxidizing agent sodium periodate (NaIO4) to the CMC-DA solution, during which the dopamine was simultaneously oxidized to polydopamine (PDA) and NaIO4 was reduced to sodium iodide (NaI). The formed NaI was encapsulated in the hydrogel and endowed the hydrogel with computerized tomography (CT) imaging ability to monitor the hydrogel degradation and the tumor therapy process. Moreover, the photosensitizer Ce6 can be loaded by the gel system via directly soaking the hydrogel in the Ce6 solution. Under the near-infrared light irradiation, Ce6 can produce cytotoxic reactive oxygen species and the PDA can produce heat to trigger the tumor PDT and PTT respectively to eradicate the tumor recurrence. In general, the designed hydrogel is biocompatible and biodegradable, has a good photothermal conversion, drug loading and CT imaging ability, which laid the foundation for the rational design of biodegradable hydrogels for multifunctional applications.