Synthesis and biological evaluation of glucagon-like peptide-1 analogs with the C-terminal helix 3 of albumin-binding domain 3.

Based on peptide 6 (Ser-GLP-1 [7-35]-GVKALIDEILAA-NH; GVKALI-DEILAA is the C-terminal helix 3 of albumin-binding domain 3 of protein G from bacterial Streptococcal G strain 148 [G148-ABD3]), a series of its analogs (compounds 0-VI: Aib-GLP-1 [7-35]-linkers-GVKALIDEILAA-NH) were designed and synthesized using microwave-assisted solid-phase synthesis. First, to monitor the reaction process and reduce potential risks, the synthesis process of compounds 0-VI was divided into three stages. Next, to explore the effect of these linkers on their albumin-binding rates, albumin-binding assays were performed.

Prognostic value of protein biomarkers in liver transplantation: A systematic review.

Liver transplantation is currently the preferred method for the treatment of advanced liver disease and early-stage hepatocellular carcinoma (HCC). Although advances in surgical techniques, immunosuppressive drugs and postoperative management have reduced the incidence of postoperative complications, how to effectively predict or diagnose postoperative complications earlier and reduce their incidence is still a clinical concern. We performed a comprehensive proteomics literature research to identified protein biomarkers in complications after liver transplantation.

Protective effects of interleukin-22 on oxalate-induced crystalline renal injury via alleviating mitochondrial damage and inflammatory response.

Oxalate-induced crystalline kidney injury is one of the most common types of crystalline nephropathy. Unfortunately, there is no effective treatment to reduce the deposition of calcium oxalate crystals and alleviate kidney damage. Thus, proactive therapeutic is urgently needed to alleviate the suffering it causes to patient.

Therapeutic efficacy and mechanism of CD73-TGFβ dual-blockade in a mouse model of triple-negative breast cancer.

Although chemotherapy and recently approved immunotherapies have improved treatment of triple-negative breast cancer (TNBC), the clinical outcome for this deadly disease remains unsatisfactory. We found that both cluster of differentiation 73 (CD73) and transforming growth factor (TGF)β were elevated in TNBC and correlated with the epithelial-mesenchymal transition (EMT), fibrotic stroma, an immune-tolerant tumor environment, and poor prognosis. To explore the efficacy of CD73-TGFβ dual-blockade, we generated a bifunctional anti-CD73-TGFβ construct consisting of the CD73 antibody MEDI9447 fused with the TGFβRII extracellular-domain (termed MEDI-TGFβR).

Efficient synthesis of Aib -Arg -GLP-1 (7-37) by liquid-phase fragment condensation.

Glucagon-like peptide-1 (GLP-1) is a potential therapeutic agent for treating Type 2 diabetes, owing to its glucose-dependent capability to stimulate insulin secretion. Semaglutide is currently the best GLP-1 analogue; however, the Aib -Arg -GLP-1 (7-37) of semaglutide contains an unnatural amino acid at the eighth position (Aib: 2-aminoisobutyric acid), which hinders its fermentation process. Aib -Arg -GLP-1 (7-37) is mainly synthesised by solid-phase synthesis.

Immunometabolism and potential targets in severe COVID-19 peripheral immune responses.

Graphical Abstract Image, graphical abstract.

Therapeutic Opportunities of IL-22 in Non-Alcoholic Fatty Liver Disease: From Molecular Mechanisms to Clinical Applications.

Nonalcoholic fatty liver disease (NAFLD) represents one of the most common liver disorders and can progress into a series of liver diseases, including nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even liver cancer. Interleukin-22 (IL-22), a member of the IL-10 family of cytokines, is predominantly produced by lymphocytes but acts exclusively on epithelial cells. IL-22 was proven to favor tissue protection and regeneration in multiple diseases.

A bispecific antibody targeting HER2 and PD-L1 inhibits tumor growth with superior efficacy.

Activation of the programmed cell death protein 1 and programmed cell death ligand 1 (PD-1/PD-L1) signaling axis plays important roles in intrinsic or acquired resistance to human epidermal growth factor receptor 2 (HER2)-directed therapies in the clinic. Therefore, therapies simultaneously targeting both HER2 and PD-1/PD-L1 signaling pathways are of great significance. Here, aiming to direct the anti-PD-L1 responses toward HER2-expressing tumor cells, we constructed a humanized bispecific IgG1 subclass antibody targeting both HER2 and PD-L1 (HER2/PD-L1; BsAb), which displayed satisfactory purity, thermostability, and serum stability.

Lowering drug prices and enhancing pharmaceutical affordability: an analysis of the national volume-based procurement (NVBP) effect in China.

To cope with the increasing healthcare costs brought about by the universal health insurance programme, national volume-based procurement (NVBP) was implemented in China to reduce drug prices. However, the impact of NVBP remains unknown. We reported the effects of the NVBP pilot programme on medication affordability and discussed the challenges and recommendations for further reforms.

A Novel Bifunctional Fusion Protein, Vunakizumab-IL22, for Protection Against Pulmonary Immune Injury Caused by Influenza Virus.

Influenza A virus infection is usually associated with acute lung injury, which is typically characterized by tracheal mucosal barrier damage and an interleukin 17A (IL-17A)-mediated inflammatory response in lung tissues. Although targeting IL-17A has been proven to be beneficial for attenuating inflammation around lung cells, it still has a limited effect on pulmonary tissue recovery after influenza A virus infection. In this research, interleukin 22 (IL-22), a cytokine involved in the repair of the pulmonary mucosal barrier, was fused to the C-terminus of the anti-IL-17A antibody vunakizumab to endow the antibody with a tissue recovery function.

Pandemic Worry and Preventive Health Behaviors During the COVID-19 Outbreak.

As schools are preparing for onsite learning, it is urgently needed to characterize the extent of pandemic worry and to examine predictors of adopting preventive health behaviors of hand washing, face mask wearing, and maintaining social distance among student pharmacists. An online survey was sent to 326 student pharmacists in the United States. Pandemic worry was measured using a seven-point Likert scale ranging from extremely not afraid of, to extremely afraid of getting COVID-19.

Design, synthesis and biological evaluation of double fatty chain-modified glucagon-like peptide-1 conjugates.

Twelve double fatty chains and Aib-Arg-GLP-1 (7-37) were designed and obtained by microwave-assisted solid-phase synthesis. Then, twelve conjugates of Aib-Arg-GLP-1 (7-37) were synthesized in 1% triethylamine aqueous solution. Conjugates 2, 3, 6, 7, 10 and 11 showed better GLP-1 receptor activation potency than semaglutide.

Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance.

Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate consisted of the HER2-targeted monoclonal antibody trastuzumab and the tubulin inhibitor emtansine, has shown potent therapeutic value in HER2-positive breast cancer (BC). However, a clinical trial indicated that T-DM1 exerts a limited effect on HER2-positive gastric cancer (GC), but the underlying mechanism is inconclusive. Our research attempted to reveal the probable mechanism and role of autophagy in T-DM1-treated HER2-positive GC.

Reversal of Multidrug Resistance by Apolipoprotein A1-Modified Doxorubicin Liposome for Breast Cancer Treatment.

Multidrug resistance (MDR) remains a major problem in cancer therapy and is characterized by the overexpression of p-glycoprotein (P-gp) efflux pump, upregulation of anti-apoptotic proteins or downregulation of pro-apoptotic proteins. In this study, an Apolipoprotein A1 (ApoA1)-modified cationic liposome containing a synthetic cationic lipid and cholesterol was developed for the delivery of a small-molecule chemotherapeutic drug, doxorubicin (Dox) to treat MDR tumor. The liposome-modified by ApoA1 was found to promote drug uptake and elicit better therapeutic effects than free Dox and liposome in MCF-7/ADR cells.

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses.

Amino Acid Degrading Enzymes and Autophagy in Cancer Therapy.

Recently, there has been renewed interest in metabolic therapy for cancer, particularly in amino acid deprivation by enzymes. L-asparaginase was approved for the treatment of acute lymphoblastic leukemia by the U.S.

An Omalizumab Biobetter Antibody With Improved Stability and Efficacy for the Treatment of Allergic Diseases.

The critical role of IgE in allergic diseases is well-documented and clinically proven. Omalizumab, a humanized anti-IgE antibody, was the first approved antibody for the treatment of allergic diseases. Nevertheless, omalizumab still has some limitations, such as product instability and dosage restriction in clinical application.

MASI: microbiota-active substance interactions database.

Xenobiotic and host active substances interact with gut microbiota to influence human health and therapeutics. Dietary, pharmaceutical, herbal and environmental substances are modified by microbiota with altered bioavailabilities, bioactivities and toxic effects. Xenobiotics also affect microbiota with health implications.

Baicalin Inhibits Influenza A Virus Infection Promotion of M1 Macrophage Polarization.

Background And Aims: The natural compound baicalin (BA) possesses potent antiviral properties against the influenza virus. However, the underlying molecular mechanisms of this antiviral activity and whether macrophages are involved remain unclear. In this study, we, therefore, investigated the effect of BA on macrophages.

Gene therapy for neurodegenerative disorders: advances, insights and prospects.

Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors, novel therapeutic targets, and reliable of delivery routes for transgenes.

Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody-Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function.

Although tyrosine kinase inhibitor therapy and immunotherapy have significantly improved lung cancer management, many patients do not benefit or become resistant to treatment, highlighting the need for novel treatments. We found elevated CD73 expression to be prevalent in non-small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial-mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance.