Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species.

The canonical transient receptor potential channel (TRPC) proteins form Ca-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model.

Effects and mechanisms of Xiaochaihu Tang against liver fibrosis: An integration of network pharmacology, molecular docking and experimental validation.

Ethnopharmacological Relevance: Liver fibrosis is a potentially harmful chronic liver disease caused by various etiologies. There is currently no specific drug for liver fibrosis. Xiaochaihu Tang (XCHT) is a traditional formula combined of seven herbs, which was first recorded in the Treatise on Febrile Diseases in Han Dynasty of ancient China.

TRPC1 contributes to endotoxemia-induced myocardial dysfunction via mediating myocardial apoptosis and autophagy.

Cardiac dysfunction is a vital complication of endotoxemia (ETM) with limited therapeutic options. Transient receptor potential canonical channel (TRPC)1 was involved in various heart diseases. While, the role of TRPC1 in ETM-induced cardiac dysfunction remains to be defined.

Old targets, new strategy: Apigenin-7-O-β-d-(-6″-p-coumaroyl)-glucopyranoside prevents endothelial ferroptosis and alleviates intestinal ischemia-reperfusion injury through HO-1 and MAO-B inhibition.

With the increasing morbidity and mortality, intestinal ischemia/reperfusion injury (IIRI) has attracted more and more attention, but there is no efficient therapeutics at present. Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new flavonoid glycoside isolated from Clematis tangutica that has strong antioxidant abilities in previous studies. However, the pharmacodynamic function and mechanism of APG on IIRI remain unknown.

Amphipathic dendritic poly-peptides carrier to deliver antisense oligonucleotides against multi-drug resistant bacteria in vitro and in vivo.

Background: Outbreaks of infection due to multidrug-resistant (MDR) bacteria, especially Gram-negative bacteria, have become a global health issue in both hospitals and communities. Antisense oligonucleotides (ASOs) based therapeutics hold a great promise for treating infections caused by MDR bacteria. However, ASOs therapeutics are strangled because of its low cell penetration efficiency caused by the high molecular weight and hydrophilicity.

Coumarin Derivative N6 as a Novel anti-hantavirus Infection Agent Targeting AKT.

Hantaviruses are globally emerging zoonotic viruses that can cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe, which is primarily caused by Hantaan virus (HTNV) infection, results in profound morbidity and mortality. However, no specific treatment is available for this disease. Coumarin derivatives have been reported as antiviral molecules, while studies about the bioactivity of coumarin derivatives against HTNV infection are limited.

Association of ABCB1 polymorphisms with carbamazepine metabolism and resistance in epilepsy: A meta-analysis.

Objective: ABCB1 polymorphisms were previously demonstrated to be associated with the metabolism and resistance of carbamazepine (CBZ) in epilepsy, but the results still remained controversial. Therefore, we performed this meta-analysis to further evaluate the impacts of ABCB1 polymorphisms on CBZ metabolism and resistance.

Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database and Wan Fang Database were searched for eligible publications up to 5 July 2021.

Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.

Canonical transient receptor potential channels (TRPCs) are nonselective, high calcium permeability cationic channels. The TRPCs family includes TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7. These channels are widely expressed in the cardiovascular and nervous systems and exist in many other human tissues and cell types, playing several crucial roles in the human physiological and pathological processes.

Loop-armed DNA tetrahedron nanoparticles for delivering antisense oligos into bacteria.

Background: Antisense oligonucleotides (ASOs) based technology is considered a potential strategy against antibiotic-resistant bacteria; however, a major obstacle to the application of ASOs is how to deliver them into bacteria effectively. DNA tetrahedra (Td) is an emerging carrier for delivering ASOs into eukaryotes, but there is limited information about Td used for bacteria. In this research, we investigated the uptake features of Td and the impact of linkage modes between ASOs and Td on gene-inhibition efficiency in bacteria.

Restoration of the Antibiotic Susceptibility of Methicillin-Resistant and Extended-Spectrum β-Lactamases Through Combination with Chelerythrine.

Multidrug resistance poses a severe threat to public health and urgently requires new solutions. The natural product chelerythrine (CHE) is a benzophenanthridine alkaloid with antimicrobial potential. In this study, CHE was effective against seven gram-positive bacterial strains, and the minimum inhibitory concentrations (MICs) ranged from 2 to 4 μg/mL.

Identification of a prolonged action molecular GLP-1R agonist for the treatment of femoral defects.

Autografts are still regarded as the gold standard treatment for bone defects but they require additional surgery that causes pain for the patient. Thus, alternatives that can substitute for grafts are required. In the present study, a novel poly-GLP-1 molecule was developed using a polymeric pro-drug strategy which was found to accelerate bone healing in a mouse femoral defect model.

PAMP protects intestine from Enterohemorrhagic Escherichia coli infection through destroying cell membrane and inhibiting inflammatory response.

Proadrenomedullin N-terminal 20 peptide (PAMP) is elevated in sepsis, but the function and possible mechanism of PAMP in bacterial infection is elusive. This study is aim to evaluate the role of PAMP in the interaction between the Enterohemorrhagic E. coli (EHEC) and the host barrier.

Synthesis of novel cellulose- based antibacterial composites of Ag nanoparticles@ metal-organic frameworks@ carboxymethylated fibers.

A novel cellulose-based antibacterial material, namely silver nanoparticles@ metal-organic frameworks@ carboxymethylated fibers composites (Ag NPs@ HKUST-1@ CFs), was synthesized. The results showed that the metal-organic frameworks (HKUST-1) were uniformly anchored on the fiber's surfaces by virtue of complexation between copper ions in HKUST-1 and carboxyl groups on the carboxymethylated fibers (CFs). The silver nanoparticles (Ag NPs) were immobilized and well-dispersed into the pores and/or onto the surfaces of HKUST-1 via in situ microwave reduction, resulting in the formation of novel Ag NPs@ HKUST-1@ CFs composites.

Heteropoly acid catalytic treatment for reactivity enhancement and viscosity control of dissolving pulp.

The reactivity enhancement and viscosity control are of practical importance during the manufacture of high-quality cellulose (also known as dissolving pulp). In the study, the concept of using phosphotungstic acid (HPW) for this purpose was demonstrated. The Fock reactivity of resultant pulp increased from 49.

Advances in the delivery of antisense oligonucleotides for combating bacterial infectious diseases.

Discovery and development of new antibacterial drugs against multidrug resistant bacterial strains have become more and more urgent. Antisense oligonucleotides (ASOs) show immense potential to control the spread of resistant microbes due to its high specificity of action, little risk to human gene expression, and easy design and synthesis to target any possible gene. However, efficient delivery of ASOs to their action sites with enough concentration remains a major obstacle, which greatly hampers their clinical application.

Exendin-4 Induces Bone Marrow Stromal Cells Migration Through Bone Marrow-Derived Macrophages Polarization via PKA-STAT3 Signaling Pathway.

Background/aims: The synthesis and degradation processes involved in bone remodeling are critically regulated by osteoblasts and osteoclasts. The GLP-1 receptor agonist Exendin-4 is beneficial for osteoblast differentiation and increases the number of osteoblasts.

Methods: We constructed an ovariectomized model to evaluate the impact of Exendin-4 on bone formation in osteoporosis.

The HRH4 rs11662595 mutation is associated with histamine H receptor dysfunction and with increased epithelial-to-mesenchymal transition progress in non-small cell lung cancer.

We previously demonstrated that histamine H receptor (HRH4) played important roles to suppress epithelial-to-mesenchymal transition (EMT) progress in non-small cell lung cancer (NSCLC). Furthermore, recent investigations suggested that genetic variations in HRH4 gene affected HRH4 function and eventually contributed to certain HRH4-related diseases. However, the relations between polymorphisms in HRH4 gene and NSCLC as well as their underlying mechanisms remain largely uninvestigated.

The Disulfide Bond of the Peptide Thanatin Is Dispensible for Its Antimicrobial Activity In Vivo and In Vitro.

Thanatin (THA) displays potent antibiotic activity, especially against extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli both in vitro and in vivo, with minimal hemolytic toxicity and satisfactory stability in plasma. However, the high cost of thanatin significantly limits its development and clinical application. To reduce the cost of peptide synthesis, a formulation of cyclic thanatin (C-thanatin) called linear thanatin (L-thanatin) was synthesized and its activity was evaluated in vivo and in vitro Results showed that C-thanatin and L-thanatin MICs did not differ against eight Gram-negative and two Gram-positive bacterial strains.

Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin.

Glucagon-like peptide 1 (GLP-1) plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4) promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model.

An Orally Active Allosteric GLP-1 Receptor Agonist Is Neuroprotective in Cellular and Rodent Models of Stroke.

Diabetes is a major risk factor for the development of stroke. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been in clinical use for the treatment of diabetes and also been reported to be neuroprotective in ischemic stroke. The quinoxaline 6,7-dichloro-2-methylsulfonyl-3-N-tert- butylaminoquinoxaline (DMB) is an agonist and allosteric modulator of the GLP-1R with the potential to increase the affinity of GLP-1 for its receptor.

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice.

Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally.

Oligomerization of RNAIII-Inhibiting Peptide Inhibits Adherence and Biofilm Formation of Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo.

Biofilm formation enhances bacterial resistance and complicates treatment. Therefore, an innovative strategy is urgently needed for the treatment of Staphylococcus aureus biofilm infectious diseases. RNAIII-inhibiting peptide (RIP), as a quorum-sensing inhibitor, inhibits S.

Efficient Transfection of Phosphorothioate Oligodeoxyribonucleotides by lipofectamine2000 into Different Bacteria.

Antisense technology has been a promising strategy for combating infectious diseases caused by multi-drug resistant bacterial strains, but the poor cellular uptake and transfection efficiency of these "antisense antibiotics" is strangling the development of antisense RNA therapeutics. This study was aimed at evaluating the cellular uptake characteristics and transfection efficiency of antisense phosphorothioate oligodeoxyribonucleotides (PS-ODN) in bacterial cells mediated by LipofectamineTM 2000 (LF2000). The size and surface morphology of LF2000/ODN nanoparticle were determined by dynamic light scattering and transmission electron microscope.

Relation of polymorphism of the histidine decarboxylase gene to chronic heart failure in Han Chinese.

Histidine decarboxylase (HDC) is a key determinant of the levels of endogenous histamine that has long been recognized to play important pathophysiological roles during development of chronic heart failure (CHF). Meanwhile, certain genetic variants in HDC gene were reported to affect the function of HDC and associated with histamine-related diseases. However, the relation between polymorphisms of HDC gene and CHF risk remains unclear.