A novel annexin dimer targets microglial phagocytosis of astrocytes to protect the brain-blood barrier after cerebral ischemia.

Despite the vital role of astrocytes in preserving blood-brain barrier (BBB) integrity, their therapeutic potential as targets in ischemic stroke-induced barrier disruption remains underexplored. We previously reported externalization of phosphatidylserine (PS) on astrocytic membranes concurrent with the emergence of PS externalization in neurons. PS externalization of astrocytes induced microglial phagocytosis of astrocytes, resulting in reduced astrocyte-vascular coupling and subsequent BBB breakdown.

Present insights into the progress in gene therapy delivery systems for central nervous system diseases.

Central nervous system (CNS) diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), spinal cord injury (SCI), and ischemic strokes and certain rare diseases, such as amyotrophic lateral sclerosis (ALS) and ataxia, present significant obstacles to treatment using conventional molecular pharmaceuticals. Gene therapy, with its ability to target previously "undruggable" proteins with high specificity and safety, is increasingly utilized in both preclinical and clinical research for CNS ailments. As our comprehension of the pathophysiology of these conditions deepens, gene therapy stands out as a versatile and promising strategy with the potential to both prevent and treat these diseases.

CircRNA-mediated regulation of cardiovascular disease.

Cardiovascular diseases (CVDs) encompass a range of disorders affecting the heart and blood vessels, such as coronary heart disease, cerebrovascular disease (e.g., stroke), peripheral arterial disease, congenital heart anomalies, deep vein thrombosis, and pulmonary embolism.

Circuit reorganization of subicular cell-type-specific interneurons in temporal lobe epilepsy.

The subiculum represents a crucial brain pivot in regulating seizure generalization in temporal lobe epilepsy (TLE), primarily through synergy of local GABAergic and long-projecting glutamatergic signaling. However, little is known about how subicular GABAergic interneurons are involved in a cell-type-specific way. Here, employing Ca fiber photometry, retrograde monosynaptic viral tracing and chemogenetics in epilepsy models of both male and female mice, we elucidate circuit reorganization patterns mediated by subicular cell-type-specific interneurons and delineate their functional disparities in seizure modulation in TLE.

Capsaicin: pharmacological applications and prospects for drug designing.

Objectives: A primary objective of this review is to summarize the evidence-based pharmacological applications of capsaicin, particularly its use to manage pain and treat various health conditions. A second goal of the review is to research how recent technological advances are improving the bioavailability and therapeutic index of capsaicin, as well as the development of novel capsaicin-mimetics that are able to enhance therapeutic responses in various human diseases.

Methods: In the review, numerous human clinical trials and preclinical studies are examined to determine how effective, safe, and optimal dosages of capsaicin can be used in pain management and therapeutic applications.

The detrimental effects and mechanisms of Orlistat in disrupting energy homeostasis and reproduction in Daphnia magna.

Orlistat (ORL) has been employed as an anti-obesity pharmaceutical for several decades. Given its low absorption rate, the majority of administered ORL is excreted into the environment with feces. It is crucial to collect scientific information regarding the possible ecological risks associated with ORL.

Dynamic profiling of intra- and extra-cellular L/D-amino acids metabolism in colorectal cell and intestinal epithelial cell.

The metabolism process of amino acids is closely related to the growth of normal and cancer cells. It is still not clear how L/D-configuration amino acids participate in the metabolism of colorectal cell. Herein, intra- and extra-cellular metabolic distribution of L/D-amino acids in colorectal cell (HCT116) and human normal intestinal epithelial cell (NCM460) were profiled utilizing HPLC-MS/MS coupled with a chiral probe.

Assessment of Efficacy Evidence for Approvals of Novel Drugs in China Between 2018 and 2022.

After the reform of China's drug review and approval system, there has been a notable increase in the number of novel drugs approved. This cross-sectional study aimed to assess the characteristics of efficacy evidence for novel drugs approved in China. This study included 240 novel drugs approved by the NMPA for 256 indications between 2018 and 2022.

Antimicrobial Peptides From Different Sources: Isolation, Purification, and Characterization to Potential Applications.

Antimicrobial peptides (AMPs) are excellent promising candidates for biomedical applications owing to their structural properties, high biocompatibility, good biodegradability, and functional diversity. Unlike conventional antibiotics, AMPs have been shown to have broad-spectrum antimicrobial activity toward Gram-positive/negative bacteria, as well as antifungal and antiviral activity. These peptides have also been found to be cytotoxic to sperm and cancer cells.

Human dose-escalation study of PET imaging CD8 T-cell infiltration in solid malignancies with [Ga]Ga -NODAGA-SNA006.

Purpose: A noninvasive method for evaluating the infiltration of CD8 T cells in tumors is urgently needed to monitor the response to immunotherapy. This study investigated the performance of a [Ga]Ga-NODAGA-SNA006 in positron emission tomography (PET) imaging of CD8 T cells in patients with solid malignancies.

Methods: This human dose-escalation PET imaging study involved eleven patients (lung cancer, 8; gastric carcinoma, 1; esophageal carcinoma, 2).

Enhancing Photothermal Therapy for Antibiofilm Wound Healing: Insights from Graphene Oxide-Cranberry Nanosheet Loaded Hydrogel in vitro, in silico, and in vivo Evaluation.

Background: Diabetic foot ulcers present a formidable challenge due to colonization by biofilm-forming microorganisms, heightened oxidative stress, and continuous wound maceration caused by excessive exudation.

Methods: To address these issues, we developed a robust, stretchable, electro-conductive, self-healing, antioxidant, and antibiofilm hydrogel. This hydrogel was synthesized through the crosslinking of polyvinyl alcohol (PVA) and chitosan (CH) with boric acid.

Chrysophanol attenuates cognitive impairment, neuroinflammation, and oxidative stress by TLR4/NFκB-Nrf2/HO-1 and BDNF/VEGF signaling in stress-intensified PTZ induced epilepsy in mice.

Background: Stress is among the most common comorbid conditions with epilepsy and a strong factor in the pathophysiology of seizures. An imbalance in neuronal circuits causes recurrent unprovoked seizures in epilepsy. Dysregulation of BDNF/VEGF expression, oxidative stress, increased levels of neuroinflammatory cytokines, and increased expression of apoptotic genes contribute to the underlying cause of the seizure.

Charge Engineering of Star-Shaped Organic Photosensitizers Enables Efficient Type-I Radicals for Photodynamic Therapy of Multidrug-Resistant Bacterial Infection.

Infection induced by multidrug-resistant bacteria is now the second most common cause of accidental death worldwide. However, identifying a high-performance strategy with good efficiency and low toxicity is still urgently needed. Antibacterial photodynamic therapy (PDT) is considered a non-invasive and efficient approach with minimal drug resistance.

Design, synthesis and investigation of biological activity and mechanism of fluoroaryl-substituted derivatives at the FL118 position 7.

Addition of fluorine atoms into chemical compounds is a validated strategy to enhance their physical, chemical and biological properties. In this study, FL118, a novel camptothecin-related small molecule known for its unique mechanism of action and superior antitumor efficacy, was utilized as a foundational drug platform. By replacing the hydrogen atom at position 7 of FL118 with a fluoroaryl group, a diverse array of FL118 derivatives were synthesized.

Podophyllotoxin mediates hepatic toxicity via the C5a/C5aR/ROS/NLRP3 and cGMP/PKG/mTOR axis in rats based on toxicological evidence chain (TEC) concept by phosphoproteomic analysis.

Background: Podophyllotoxin (PPT), a highly active compound extracted from the rhizome of Dysosma versipellis (DV), has been used as an effective anti-cancer drug clinically since the 1950s. It possesses various biological activities, including antiviral and antitumor effects. However, its clinical application is severely limited due to its hepatotoxicity, and the underlying mechanisms remain unclear.

Epiberberine ameliorates MNNG-induced chronic atrophic gastritis by acting on the EGFR-IL33 axis.

Chronic atrophic gastritis (CAG) is a prevalent form of chronic gastritis that presents with chronic inflammation of the gastric mucosa, localised gastric mucosal glandular atrophy and intestinal metaplasia. Despite the existence of diagnostic criteria, effective therapeutic strategies for this condition remain to be developed. The objective of this study was to examine the potential therapeutic benefits of epiberberine in mitigating MNNG-induced CAG and to elucidate the underlying mechanisms.

Extracellular vesicles for delivering therapeutic agents in ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is marked by the restriction and subsequent restoration of blood supply to an organ. This process can exacerbate the initial tissue damage, leading to further disorders, disability, and even death. Extracellular vesicles (EVs) are crucial in cell communication by releasing cargo that regulates the physiological state of recipient cells.

Structure Elucidation of New Kavalactone Dimers From Alpinia zerumbet Pericarps Using NMR Calculations.

Alpinia zerumbet (Pers.) B.L.

Mesogenic Architectures for Advanced Drug Delivery: Interrogating Lyotropic and Thermotropic Liquid Crystals.

The possibility of precisely regulating and targeting drug release with mesophase or Liquid crystal drug delivery systems has drawn much attention recently. This review offers a thorough investigation of liquid crystal drug delivery systems with an emphasis on their mesogenic architecture. It describes the various liquid crystal forms such as thermotropic and lyotropic liquid crystals and their applicability in advanced drug delivery.

Antibacterial betaine modified chitosan-based hydrogel with angiogenic property for photothermal enhanced diabetic wound repairing.

Chronic diabetes wound repairing is still a huge challenge in clinical practice. High concentration of reactive oxygen species and vascular disfunction are the main factors hindering the recovery of diabetes wounds. This research grafted betaine onto chitosan (CSBT) to enhance the antibacterial property and the CSBT was cross-linked with PEO dialdehyde (PEO DA) to prepare hydrogel with Ca loading to promote the coagulation.