Dihydrotanshinone I Attenuates Diet-Induced Nonalcoholic Fatty Liver Disease via Up-Regulation of IRG1.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, but effective therapeutic drugs are still lacking. Dihydrotanshinone I (DHTS), a natural product isolated from Salvia miltiorrhiza , has been shown to have ameliorative effects on NAFLD. The aim of this study was to investigate the hepatoprotective effect of DHTS on NAFLD and its mechanism.

Asymmetrically PEGylated and amphipathic heptamethine indocyanine dyes potentiate radiotherapy of renal cell carcinoma via mitochondrial targeting.

Enhancing the sensitivity of radiotherapy (RT) towards renal cell carcinoma (RCC) remains a challenge because RCC is a radioresistant tumor. In this work, we design and report asymmetrically Polyethylene Glycol (PEG)ylated and amphipathic heptamethine indocyanine dyes for efficient radiosensitization of RCC treatment. They were synthesized by modifying different lengths of PEG chains as hydrophilic moieties on one N-alkyl chain of a mitochondria-targeting heptamethine indocyanine dye (IR-808), and a radiosensitizer 2-nitroimidazole (NM) as a hydrophobic moiety on another N-alkyl chain.

A Mitochondria-Targeted Heptamethine Indocyanine Small Molecular Chelator for Attenuating Uranium Nephrotoxicity.

Radionuclide uranium has both a chemical and radioactive toxicity, leading to severe nephrotoxicity as it predominantly deposits itself in the kidneys after entering into human bodies. It crosses renal cell membranes, accumulates in mitochondria and causes mitochondrial oxidative damage and dysfunction. In this study, a mitochondria-targeted heptamethine indocyanine small molecule chelator modified with gallic acid (IR-82) is synthesized for uranium detoxication.

Stepwise increase of fidaxomicin in an engineered heterologous host through multi-level metabolic engineering.

The anti- infection (CDI) drug fidaxomicin is a natural polyketide metabolite mainly produced by , such as , , and . In the present study, we employed a stepwise strategy by combining heterologous expression, chassis construction, promoter engineering, activator and transporters overexpression, and optimization of fermentation media for high-level production of fidaxomicin. The maximum yield of 384 mg/L fidaxomicin was achieved with engineered D7-VHb in 5 L-tank bioreactor, and it was approximately 15-fold higher than the native strain YP-1 with higher strain stability and growth rate.

Ginkgolide C attenuated Western diet-induced non-alcoholic fatty liver disease via increasing AMPK activation.

Background: Non-alcoholic steatohepatitis (NASH) is a metabolic dysregulation-related disorder that is generally characterized by lipid metabolism dysfunction and an excessive inflammatory response. Currently, there are no authorized pharmacological interventions specifically designed to manage NASH. It has been reported that Ginkgolide C exhibits anti-inflammatory effects and modulates lipid metabolism.

Rational construction of a high-quality and high-efficiency biosynthetic system and fermentation optimization for A82846B based on combinatorial strategies in Amycolatopsis orientalis.

Background: Oritavancin is a new generation of semi-synthetic glycopeptide antibiotics against Gram-positive bacteria, which served as the first and only antibiotic with a single-dose therapeutic regimen to treat ABSSSI. A naturally occurring glycopeptide A82846B is the direct precursor of oritavancin. However, its application has been hampered by low yields and homologous impurities.

Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4).

A Mitochondria-Targeted Ferroptosis Inducer Activated by Glutathione-Responsive Imaging and Depletion for Triple Negative Breast Cancer Theranostics.

Ferroptosis is a new type of iron-dependent programmed cell death characterized by glutathione (GSH) depletion, selenoprotein glutathione peroxidase 4 (GPX4) inactivation, and lipid peroxides accumulation. Mitochondria, as the main source of intracellular energy supply and reactive oxygen species (ROS) generation, play a central role in oxidative phosphorylation and redox homeostasis. Therefore, targeting cancer-cell mitochondria and attacking redox homeostasis is expected to induce robust ferroptosis-mediated anticancer effects.

Rationally Designed Heptamethine Cyanine Photosensitizers that Amplify Tumor-Specific Endoplasmic Reticulum Stress and Boost Antitumor Immunity.

Cancer phototherapy activates immunogenic cell death (ICD) and elicits a systemic antitumor immune response, which is an emerging approach for tumor treatment. Most available photosensitizers require a combination of immune adjuvants or checkpoint inhibitors to trigger antitumor immunity because of the immunosuppressive tumor microenvironment and the limited phototherapeutic effect. A class of tumor-targeting heptamethine cyanine photosensitizers modified with an endoplasmic reticulum (ER)-targeting group (benzenesulfonamide) are synthesized.

Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury.

Wound healing is seriously retarded when combined with ionizing radiation injury, because radiation-induced excessive reactive oxygen species (ROS) profoundly affect cell growth and wound healing. Mitochondria play vital roles not only as cellular energy factories but also as the main source of endogenous ROS, and in this work a mitochondria-targeting radioprotectant (CY-TMP1) is reported for radiation injury-combined wound repair. It was designed, synthesized and screened out from different conjugates between mitochondria-targeting heptamethine cyanine dyes and a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (TEMPO).

Synthesis of a versatile mitochondria-targeting small molecule for cancer near-infrared fluorescent imaging and radio/photodynamic/photothermal synergistic therapies.

Although as a mainstay modal for cancer treatment, the clinical effect of radiotherapy (RT) does not yet meet the need of cancer patients. Developing tumour-preferential radiosensitizers or combining RT with other treatments has been acknowledged highly necessary to enhance the efficacy of RT. The present study reported a multifunctional bioactive small-molecule (designated as IR-83) simultaneously exhibiting tumour-preferential accumulation, near-infrared imaging and radio/photodynamic/photothermal therapeutic effects.

Hsa_circRNA_100146 Promotes Prostate Cancer Progression by Upregulating TRIP13 Sponging miR-615-5p.

This study was conducted for investigating the functions of circular RNA circRNA_100146 (circRNA_100146) in the development of prostate cancer (PCa) and identifying the underlying mechanisms of the circRNA_100146/miR-615-5p/TRIP13 axis. Under the support of RT-PCR, the expression of circRNA_100146 in PCa cells was examined. Cell Counting Kit-8 (CCK-8) assays and clone formation assays were applied to the assessment of cell proliferation.

Rational engineering strategies for achieving high-yield, high-quality and high-stability of natural product production in actinomycetes.

Actinomycetes are recognized as excellent producers of microbial natural products, which have a wide range of applications, especially in medicine, agriculture and stockbreeding. The three main indexes of industrialization (titer, purity and stability) must be taken into overall consideration in the manufacturing process of natural products. Over the past decades, synthetic biology techniques have expedited the development of industrially competitive strains with excellent performances.

Genome-based rational engineering of Actinoplanes deccanensis for improving fidaxomicin production and genetic stability.

Microbial fermentation is currently still the major way to produce structural complicated clinical drugs. Yet, the low productivity and genetic instability of producing strains remain the bottlenecks in microbial pharmaceutical industry. Fidaxomicin is a microbial drug against the Clostridium difficile infection.

Synthesis of Mitochondria-Anchored Nitroimidazoles with a Versatile NIR Fluorophore for Hypoxic Tumor-Targeting Imaging and Chemoradiotherapy.

Nitroimidazoles are one of the most common radiosensitizers investigated to combat hypoxia-induced resistance to cancer radiotherapy. However, due to poor selectivity distinguishing cancer cells from normal cells, effective doses of radiosensitization are much closer to the doses of toxicity induced by nitroimidazoles, limiting their clinical application. In this work, a tumor-targeting near-infrared (NIR) cyanine dye (IR-808) was utilized as a targeting ligand and an NIR fluorophore tracer to chemically conjugate with different structures of hypoxia-affinic nitroimidazoles.

Anticancer effects of Mahanimbine alkaloid on the human bladder cancer cells are due to the induction of G0/G1 cell cycle arrest, apoptosis and autophagy.

Purpose: The main purpose of the current research work was to investigate the anticancer effects of Mahanimbine alkaloid in human bladder cancer cells along with examining its effects on cellular apoptosis, cell cycle phase distribution, and cell autophagy.

Methods: Cell viability was examined by WST-1 cell viability assay. Mahanimbine-induced apoptosis was examined by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) staining as well as using flow cytometry in combination with annexin-v/propidium iodide (PI) staining.

Comprehensive dissection of dispensable genomic regions in Streptomyces based on comparative analysis approach.

Background: Large-scale genome reduction has been performed to significantly improve the performance of microbial chassis. Identification of the essential or dispensable genes is pivotal for genome reduction to avoid synthetic lethality. Here, taking Streptomyces as an example, we developed a combinatorial strategy for systematic identification of large and dispensable genomic regions in Streptomyces based on multi-omics approaches.

Study on the ArI-catalyzed intramolecular oxy-cyclization of 2-alkenylbenzamides to benzoiminolactones.

A new intramolecular oxy-cyclization of 2-alkenylbenzamides catalyzed by ArI has been developed. This protocol is highlighted by its metal-free catalytic system and extremely short reaction time, providing efficient and straightforward access to various benzoiminolactones in good to excellent yields. Interestingly, a regioselective transformation occurred when using two different reaction systems.

Inhibition of endogenous hydrogen sulfide production exacerbates the inflammatory response during urine-derived sepsis-induced kidney injury.

The aim of the present study was to investigate the effects of endogenous HS on the inflammatory response in kidneys following urine-derived sepsis-induced injury. A rabbit model of urine-derived sepsis was established by injecting into the ligated ureter. Rabbits were randomly divided into the, control, sham, sepsis and DL-propargylglycine (PAG)-treated sepsis groups.

Theoretical study of the intermolecular recognition mechanism between Survivin and substrate based on conserved binding mode analysis.

Survivin is the smallest member of IAP (inhibitor of apoptosis protein) family, which plays important roles in both mitosis and apoptosis. It has become an attractive drug target due to its overexpression in many human cancers. Survivin has been proven to bind to Smac/DIABLO protein that indirectly inhibits apoptosis.

Efficacy and safety of carbon dioxide insufflation versus air insufflation for endoscopic retrograde cholangiopancreatography: A meta-analysis update.

Background And Objective: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for visualising the biliary tree and pancreatic ducts, and carbon dioxide (CO) insufflation during ERCP is considered an alternative technique to air insufflation for relieving post-procedural abdominal discomfort (abdominal pain and distension). The aim of the present study was to evaluate the effect of CO insufflation on the remission of abdominal discomfort and the potential side effects by conducting a meta-analysis.

Methods: The method recommended by the Cochrane Collaboration was employed to conduct a meta-analysis of randomised controlled trials (RCTs) of CO insufflation versus air insufflation during ERCP.

Hydrogen sulfide reduces kidney injury due to urinary-derived sepsis by inhibiting NF-κB expression, decreasing TNF-α levels and increasing IL-10 levels.

The present study aimed to investigate the effect of hydrogen sulfide (HS) on kidney injury induced by urinary-derived sepsis. Rabbits were randomly divided into control, sham, sepsis, NaHS 2.8 μmol/kg and NaHS 8.

Ulinastatin reduces urinary sepsis‑related inflammation by upregulating IL‑10 and downregulating TNF‑α levels.

The aim of the present study was to determine the efficacy of ulinastatin (UTI) for the treatment of sepsis and to investigate the associated molecular mechanisms. Twenty‑four male rabbits were randomly divided into 4 groups, the normal, sham, sepsis model and UTI groups, each containing 6 rabbits. Serum levels of interleukin (IL)‑10 and tumor necrosis factor‑α (TNF‑α) were measured by enzyme‑linked immunosorbent assay (ELISA).

β-elemene acts as an antitumor factor and downregulates the expression of survivin, Bcl-xL and Mta-1.

β-elemene, a non-cellular antineoplastic agent, may be used to effectively inhibit the growth and proliferation of various types of tumor cells by inhibiting the nucleic acid synthesis or inducing their apoptosis and differentiation. The aim of this study was to investigate the expression, as well as the effects, of Mta-1, survivin and Bcl-xL in T24 bladder cancer cells following β-elemene treatment. The expression of the three proteins in T24 cells following β-elemene treatment was analyzed by immunocytochemistry staining and western blot analysis.