Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1.

Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG's function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.

Clinical therapeutic effects of eradication of Helicobacter pylori in treating patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis.

BACKGROUND: Previous studies have demonstrated that Helicobacter pylori is a critical factor in the development of gastrointestinal diseases. However, only limited studies have reported results on the relationship between H pylori infection and patients with type 2 diabetes mellitus (T2DM). Moreover, the conclusions from these past studies are variable. Because there are contradictory results on this issue, the present study aims to examine the clinical therapeutic impacts of H pylori eradication to treat patients experiencing T2DM. METHODS: The present protocol is drafted according to the provisions of the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols guidelines. PubMed, Cochrane Central Register of Controlled Trials databases, EMBASE, Web of Science, China National Knowledge Infrastructure, and Chinese BioMedical Literature Database will be searched up to May 2021 to obtain randomized controlled trials evaluating the clinical therapeutic effects of H pylori eradication to treat patients experiencing T2DM. We will use 2 investigators independently to carry out study selection, data extraction, and employ the Cochrane Collaboration criteria to evaluate their risks of bias. Furthermore, we will apply Stata 16.0 software to perform data analysis. RESULTS: We intend to evaluate the clinical therapeutic impacts of H pylori eradication to treat patients suffering from T2DM. CONCLUSIONS: Our findings may support existing evidence on the clinical therapeutic impacts of H pylori eradication to treat patients with T2DM. ETHICS AND DISSEMINATION: Since all data will be extracted from the published literature, the study does not require an ethical approval. OSF REGISTRATION NUMBER: May 31, 2021.osf.io/qtexu. (https://osf.io/qtexu/).

Cyclocurcumin, a curcumin derivative, exhibits immune-modulating ability and is a potential compound for the treatment of rheumatoid arthritis as predicted by the MM-PBSA method.

The control and treatment of rheumatoid arthritis is a challenge in today's world. Therefore, the pursuit of natural disease-modifying antirheumatic drugs (DMRDs) remains a top priority in rheumatology. The present study focused on curcumin and its derivatives in the search for new DMRDs. We focused on prominent p38 mitogen-activated protein (MAP) kinase p38α which is a prime regulator of tumor necrosis factor-α (TNF-α), a key mediator of rheumatoid arthritis. In the present study, we used the X-ray crystallographic structure of p38α for molecular docking simulations and molecular dynamic simulations to study the binding modes of curcumin and its derivatives with the active site of p38α. The ATP-binding domain was used for evaluating curcumin and its derivatives. Molecular docking simulation results were used to select 4 out of 8 compounds. These 4 compounds were simulated using GROMACS molecular simulation platform; the results generated were subjected to molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) calculations. The results showed cyclocurcumin as a potential natural compound for development of a potent DMRD. These data were further supported by inhibition of TNF-α release from lipopolysaccharide (LPS)-stimulated human macrophages following cyclocurcumin treatment.

Kinetic study of pentosan solubility during heating and reacting processes of steam treatment of green bamboo.

Green bamboo was hydrolyzed over a range of durations at different temperatures. A simple pseudo-homogeneous irreversible first order kinetic model was developed to describe pentosan solubility during steam treatment of green bamboo. To avoid the influence of soluble pentosan during heating process, kinetic parameters were effectively dissolved based on the data in the reacting process. Moreover, the pentosan solubility during heating process was also well modeled by numerical algorithm method. According to the origin of H factor, a modified parameter called steam treatment factor (f(P)) was proposed in this paper based on the determined kinetic constants. Finally, residual pentosan in whole process could be predicted properly based on the f(P) and the introducing of potential hydrolysis degree (h(d)). After using f(P) to combine reaction temperature and time into a single factor, comparative result showed that steam treatment is more effective for removing pentosan compared with hot water extraction.