Strategies to develop polymeric microneedles for controlled drug release.

The remarkable appeal of microneedle controlled-release systems has captivated both the academic community and pharmaceutical industry due to their great potential for achieving spatiotemporally controlled release, coupled with their the minimally invasive nature and ease of application. Over the years, scientists have dedicated their efforts to advancing microneedle systems by manipulating the physicochemical properties of matrix materials, refining microneedle designs, and interfacing with external devices to provide tailored drug release profiles in a spatiotemporally controllable manner. Expanding upon our understanding of drug release mechanisms from polymeric microneedles, which include diffusion, swelling, degradation, triggering, and targeting, there is a growing focus on manipulating the location and rate of drug release through innovative microneedle designs.

Sappanone A ameliorates acute lung injury through inhibiting the activation of the NF-κB signaling pathway.

Acute lung injury (ALI) is a serious respiratory disease characterized by diffuse alveolar injury, and it has emerged as a major concern in clinical practice due to limited treatments. This study aimed to explore the pharmacological effects and regulatory mechanism of sappanone A (SA) on ALI. In vivo, mice were administered with SA followed by intratracheal injection of lipopolysaccharide (LPS) to establish an animal model of ALI.

Interaction of PASTICCINO2 with Golgi anti-apoptotic proteins confers resistance to endoplasmic reticulum stress and is dependent on very-long-chain fatty acids.

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore the homeostasis of the ER when it is under stress; however, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis GOLGI ANTI-APOPTOTIC PROTEINS (GAAPs) are involved in resisting ER stress, and in this study, we found that PASTICCINO2 (PAS2), which is involved in very-long-chain fatty acid (VLCFA) synthesis, interacts with GAAPs and INOSITOL REQUIRING ENZYME 1.

GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

Background: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro.

Methods: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 μg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight.

One-step gene knock-out in porcine embryos using recombinant adeno-associated viruses.

Gene-edited pigs have become prominent models for studying human disease mechanisms, gene therapy, and xenotransplantation. CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated 9 (CRISPR/Cas9) technology is a widely employed tool for generating gene-edited pigs. Nevertheless, delivering CRISPR/Cas9 to pre-implantation embryos has traditionally posed challenges due to its reliance on intricate micromanipulation equipment and specialized techniques, resulting in high costs and time-consuming procedures.

A novel HDAC6 inhibitor attenuate APAP-induced liver injury by regulating MDH1-mediated oxidative stress.

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated.

Emission Wavelength-Tunable Bicyclic Dioxetane Chemiluminescent Probes for Precise and Imaging.

Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm.

Isolation of Projection-Specific and Behavior-Relevant Amygdala Circuit for RNA Sequencing.

One of the most sought-after topics in neuroscience is to understand how the environment regulates the activity and function of neural circuitry and subsequently influences relevant behaviors. In response to alterations in the environment, the neural circuits undergo adaptive changes ranging from gene expression changes to altered cellular function. Performing sequencing of the transcriptome involved in these behavior-related circuits will provide clues to accurately dissect the detailed mechanisms of related behavior.

Silver-Catalyzed Decarboxylative Acylation of Isocyanides Accesses to α-Ketoamides with Air as a Sole Oxidant.

α-Ketoamide moieties, as privileged units, may represent a valuable option to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with isocyanides was developed to derivatize the α-ketoamide functional group via a multicomponent reaction (MCR) cascade sequence in one pot. A series of α-ketoamides was synthesized with three components of isocyanides, aromatic α-oxocarboxylic acid analogues and water in moderate yields.

Ni-Catalyzed Protecting Group Free Diphenic Acid Analog Synthesis.

Severe side effects and drug resistance are major drawbacks of Pt-based chemotherapy in clinical practice, leading to the search for new Pt-based drugs through the tuning of coordination ligands. Therefore, seeking appropriate ligands has attracted significant interest in this area. In this study, we report a Ni-catalyzed coupling strategy for the divergent synthesis of diphenic acid derivatives and the application of these newly prepared acids in Pt(II) agent synthesis.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1.

Hydroquinone cream-based polymer microneedle roller for the combined treatment of large-area chloasma.

Melasma is a common hyperpigmented skin condition that occurs on the face and other areas prone to light exposure, seriously affecting people's quality of life. Microneedle, a new type of transdermal drug delivery device, can significantly improve skin permeability. In this study, we designed and fabricated a polymer microneedle roller (PMR) using a mold hot pressing method, and established a mouse model of melasma induced by ultraviolet radiation.

Glucagon-Like Peptide-2 Ameliorates Age-Associated Bone Loss and Gut Barrier Dysfunction in Senescence-Accelerated Mouse Prone 6 Mice.

Introduction: Senile osteoporosis is one of the most common age-related diseases worldwide. Glucagon like peptide-2 (GLP-2), a naturally occurring gastrointestinal peptide, possesses therapeutic effects on bone loss in postmenopausal women and ovariectomized rats. However, the role of GLP-2 in senile osteoporosis and underlying mechanisms has not been explored.

Subcutaneous Implantable Microneedle System for the Treatment of Alzheimer's Disease by Delivering Donepezil.

To alleviate the dilemma of drug administration in Alzheimer's disease (AD) patients, it is of great significance to develop a new drug delivery system. In this study, a subcutaneously implanted microneedle (MN) device with a swellable gelatin methacryloyl (GelMA) needle body and a dissolvable polyvinyl alcohol (PVA) backing layer was designed. The backing layer quickly dissolved once the MN was introduced into the subcutaneous, and the hydrogel needles were implanted in the subcutaneous to enable prolonged drug release.

Thermosensitive hydrogel microneedles for controlled transdermal drug delivery.

By using the prominent merit of poly(N-isopropylacrylamide) (PNIPAm) that can reversibly switch from a linear state to a coiled state with the change in temperature, in this work, gelatin was grafted with carboxylic end-capped PNIPAm as the matrix material to fabricate a physical entanglement crosslinked hydrogel microneedles (MNs) patch that can control drug release after application on the skin. The crystallization of the drug during the fabrication process of MNs was decreased due to the thermo-reversible sol-gel transition of the matrix materials. In addition, to increase the mechanical strength of the MNs and to decrease the application time, the gelatin-g-PNIPAm (GP) MNs patch was mounted onto solid MNs to fabricate a rapidly separating MNs system (RS-GP-MNs).

An update on biomaterials as microneedle matrixes for biomedical applications.

Microneedles (MNs) have been developed for various applications such as drug delivery, cosmetics, diagnosis, and biosensing. To meet the requirements of MNs used in these areas, numerous materials have been used for the fabrication of MNs. However, MNs will be exposed to skin tissues after piercing the stratum corneum barrier.

Golgi anti-apoptotic proteins redundantly counteract cell death by inhibiting production of reactive oxygen species under endoplasmic reticulum stress.

Maintaining proteostasis in the endoplasmic reticulum (ER) is critical for cell viability and plant survival under adverse conditions. The unfolded protein response (UPR) pathways interact with reactive oxygen species (ROS) to precisely trigger adaptive outputs or cell death under ER stress with varying degrees. However, little information is known about the relationship between UPR signalling and ROS regulation.

E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.

Background And Aims: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear.

Approach And Results: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity.

Endocarditis and systemic embolization from Whipple's disease.

Whipple's disease (WD), caused by infection with the organism , is a rare disease that classically presents with diarrhea, weight loss, and polyarthralgia. Less commonly, Whipple's Disease can presentation with endocarditis or neurologic infections. The authors report a patient with Whipple's Disease endocarditis whose initial presentation was acute lower extremity arterial occlusion, and review current literature regarding the epidemiology, diagnosis, treatment, and prognosis of Whipple's Disease endocarditis.

Customizable design strategies for high-performance bioanodes in bioelectrochemical systems.

Bioelectrochemical systems (BESs) can fulfill the demand for renewable energy and wastewater treatment but still face significant challenges to improve their overall performance. Core efforts have been made to enhance the bioelectrode performance, yet, previous approaches are fragmented and have limited applicability, unable to flexibly adjust physicochemical and structural properties of electrodes for specific requirements in various applications. Here, we propose a facile electrode design strategy that integrates three-dimensional printing technology and functionalized modular electrode materials.