Covalent JAK3 inhibitors based on 2-arylamino and 7H-pyrrolo[2,3-d]pyrimidine scaffold: design, synthesis, and biological evaluation for the potential treatment of bortezomib-resistant multiple myeloma.

To describe the proposed mechanism of action of shock wave therapy and discuss treatment considerations and guidelines for use in equine and canine practice. Client-owned animals with owner consent. Shock wave therapy is proposed to stimulate healing by generating forces that cause cells to undergo microtrauma and release anti-inflammatory cytokines and growth factors into the treated tissues. While the 4 types of shock wave therapies are discussed, electrohydraulic and piezoelectric are described in detail, as they are most utilized in veterinary medicine for the treatment of tendon and ligament injuries, osteoarthritis, and nonunion fractures. The dose that is applied per patient is relative to the selected settings of depth, energy level, and number of pulses delivered. It is important to recognize that the highest energy deposition and greatest biological effects are seen at anatomic regions of differing tissue types such as bone and soft tissue interfaces; thus, shock wave is particularly useful at areas of enthesopathy. Because of the mechanism of action, the use of anti-inflammatory medications and/or cryotherapy around shock wave treatment times should be avoided. Additionally, because of the potent analgesic effects of shock wave for the first 48 hours after treatment, rest is recommended to prevent any further damage to the tissues. Competition rules surrounding the use of shock wave must also be followed and discussed with owners. Shock wave therapy is an accessible and useful modality for the treatment of tendon and ligament injuries, osteoarthritis, and nonunion fractures.

Shaoyao Gancao Decoction ameliorates rheumatoid arthritis via inhibition of TNF-α/NF-κB signaling pathway.

Advances in the regulation of NLRP3 inflammasome by natural polysaccharides: Structural features, mechanisms of action, and disease associations.

The anti-obesity potential of Cassiae Semen: A review based on ethnopharmacology and modern pharmacology.

To evaluate in vitro the antifungal activity, mechanism of action, drug association, and anti-biofilm effect of the essential oil of Lippia sidoides Cham. (EO-LS) against Candida albicans and Candida auris. EO-LS was extracted, and its chemical profile was determined by GC-MS. Assays were performed to determine the Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC), mechanism of action, drug interaction with nystatin and ketoconazole, time-kill kinetics, and biofilm inhibition by confocal microscopy. The compound exhibited fungicidal activity, with MIC and MFC values of 125 µg/mL against C. albicans and 62.5 µg/mL against C. auris. The exogenous ergosterol assay indicated that EO-LS exerts antifungal activity by interfering with fungal plasma membrane functions. The combination of EO-LS with ketoconazole demonstrated pharmacological synergism, while its combination with nystatin resulted in an antagonistic effect. EO-LS significantly inhibited fungal growth (p < 0.005) and promoted a marked reduction of mature C. auris biofilm at a concentration of 125 µg/mL (p < 0.0001), as confirmed by confocal microscopy imaging. The essential oil of Lippia sidoides exhibits antifungal activity against Candida spp., including C. auris, likely through an action on the cell membrane, and shows potential as an anti-biofilm agent with pharmacological synergism when combined with ketoconazole.

Intraoperative hemostasis and dural closure are critical components of neurosurgical procedures, directly affecting operative time, blood loss, neurological outcomes, and the risk of cerebrospinal fluid leak, infection, and reoperation. Over the past 2 decades, there has been rapid expansion in the availability of hemostatic adjuncts, dural substitutes, and liquid sealants. Despite widespread adoption, product selection is frequently guided by surgeon preference and institutional practice rather than a detailed understanding of material composition, mechanism of action, and product-specific limitations. This qualitative review provides a neurosurgery-focused, product-level comparison of commonly used intraoperative hemostatic agents, dural substitutes, and dural sealants, with emphasis on composition, mechanism of action, indications, advantages, limitations, safety considerations, and cost. A comprehensive literature search was conducted using PubMed, Embase, United States Food and Drug Administration device summaries, manufacturer instructions for use, and key clinical trials and observational studies. Products were categorized into 3 groups: intraoperative hemostatic adjuncts, dural substitutes and graft materials, and liquid dural sealants and adhesives. The review encompasses gelatin-based products, oxidized regenerated cellulose, collagen-based agents, flowable gelatin-thrombin matrices, topical thrombin preparations, autologous and nonautologous dural grafts, and fibrin- and polyethylene glycol-based sealants. Selection of these materials should be guided by anatomic considerations, patient-specific factors, and best available evidence. This review serves as a practical reference to support informed intraoperative decision-making in neurosurgical practice.

The global prevalence of gout continues to rise. Baxian Huazhuo Decoction (BHD) has demonstrated significant efficacy in the clinical treatment of acute gouty arthritis (AGA); however, its mechanism of action remains unclear. This study first employed network pharmacology analysis to identify the key components, targets, and pathways of BHD against AGA. Molecular docking studies validated the binding affinity between the components of BHD and their potential targets. Ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) was utilized to identify the active components in BHD and elucidate their fragmentation pathways. Subsequently, a monosodium urate crystal-induced AGA rabbit model was established to evaluate the invivo therapeutic efficacy of BHD. The results revealed 62 predicted active components and 268 target molecules in BHD, identifying core constituents such as gentiopicroside, limonin, and indirubin, which exhibited high affinity for targets including MAPK1, PPARG, and IL-6. Invivo experiments confirmed that BHD significantly suppressed the phosphorylation of MAPK1, reduced the levels of pro-inflammatory factors such as TNF-α and IL-6, mitigated synovial damage, and inhibited the activation of the PI3K-Akt signaling pathway. This study systematically elucidates the pharmacological basis and mechanisms of action of BHD in the treatment of AGA, providing a scientific basis for its clinical application.

Orally engineered liver-targeted garlic exosome-like nanovesicles for astaxanthin precise delivery against alcoholic liver disease in mice.

Glaucocalyxin D (GLD), an ent-kaurane diterpenoid isolated from Isodon species, exhibits extensive pharmacological potential; however, its mechanism of action against acute myeloid leukemia (AML) remains to be elucidated. The present study employed a combined network pharmacology and experimental approach to elucidate the anti-AML mechanisms of GLD. Potential targets were identified using database mining and a protein-protein interaction network was constructed. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted the JAK-STAT signaling pathway as central to action by GLD. Molecular docking predicted stable binding of GLD to core targets, including STAT3. Experimental validation in HEL and K562 AML cells demonstrated that GLD potently and dose-dependently inhibits cell proliferation, with efficacy similar to the standard chemotherapeutic agent doxorubicin. Mechanistically, GLD suppressed the phosphorylation of JAK2 and STAT3. GLD also induced mitochondrial apoptosis by modulating the Bcl-2/Bax ratio and triggered G2/M phase arrest by downregulating cyclin B1 and CDK1. These findings delineated a coherent mechanism whereby GLD exerts anti-leukemic effects by inhibiting the JAK-STAT pathway, supporting its potential as a novel lead compound for AML therapy in the future.

Alisol B as a novel inhibitor of TβRs suppresses the growth and metastasis of non-small cell lung cancer by inhibiting TGF-β-induced epithelial-mesenchymal transition.

Innate immunity and biomarkers of multiple sclerosis relapse versus remission.

Shugananshen recipe improves insomnia in humans and alleviates anxiety in rats by altering expressions of key signaling molecules

Yanxiao Di'naer decoction attenuates metabolic dysfunction-associated steatohepatitis through the regulation of gut microbiota and the metabolism of bile acid.

The potential of food-derived bioactive peptides in managing sarcopenia: Identification, structure, mechanism of action, clinical perspective, practical and safety considerations

Di-tert-Butylphenol (2,4-DTBP) and its analogs disrupt thyroid hormone signaling via activation of retinoid X receptor α.

Hematologic malignancies remain a significant public health concern in the United States, affecting over 1.5 million individuals. Although chemotherapy remains a foundational component of treatment, the emergence of novel therapeutic strategies has transformed the treatment landscape. This review examines the development, mechanism of action, expanding clinical applications, and barriers to care associated with chimeric antigen receptor T-cell (CAR T-cell) therapy. Relevant data was found via a literature search across major biomedical databases focusing on current clinical implementation of CAR T-cell therapies. To date, seven CAR T-cell therapies have received U.S. Food and Drug Administration approval, demonstrating robust response rates and effective clearance of malignant cells in hematologic malignancies, including B-cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia. Despite these promising outcomes, CAR T-cell therapy faces significant challenges, including manufacturing timelines, geographic access limitations, and substantial financial burden. As the field continues to evolve, this review aims to provide clinicians with an updated synthesis of clinical outcomes, treatment-related toxicities, and persistent barriers to equitable access.

Ticks, infamous vectors of various pathogens, have evolved a unique strategy of saliva secretion during long-term feeding to suppress host defense mechanisms, including immune responses. This phenomenon may be a potential strategy to treat immune disorders and other diseases, offering a promising opportunity for exploiting parasite biology and parasite-derived molecules in drug discovery. This review examines the therapeutic potential of components in tick saliva, focusing on their mechanisms of action and clinical applications. It also discusses tick-derived immunomodulators, such as chemokine-binding proteins and complement inhibitors, that are currently attracting attention from the perspective of therapeutic drug development. Specifically, Ornithodoros moubata complement inhibitor (nomacopan), a C5 complement inhibitor contained in saliva from the soft tick O. moubata, has reached Phase III clinical trial status for hematopoietic stem cell transplantation-associated thrombotic microangiopathy and is considered an advanced research model in tick-derived drug development. The diverse and potent immunomodulatory properties of tick saliva molecules make them a potentially rich source for the identification and development of novel therapeutics, particularly for immune-mediated diseases.

Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system, which play an irreplaceable role in modulating neuronal excitability and signal transduction. This review comprehensively analyzes the molecular mechanisms and pathophysiological significance of voltage-gated sodium channels, with particular emphasis on elucidating the molecular-action mechanisms of the distinct subtypes of these channels, including Nav1.1, Nav1.2, and Nav1.6, across various neurological disorders such as familial hemiplegic migraine, epilepsy, autism spectrum disorder, and retinal dysfunction. This review also provides a comprehensive overview of the pathogenic mechanisms associated with voltage-gated sodium channels, and systematically clarifies the evolutionary pathway of treatment strategies from conventional to innovative approaches. It analyzes two major categories of conventional sodium channel blockers and their applications: antiepileptic drugs (such as carbamazepine, lamotrigine, and phenytoin) and antiarrhythmic drugs (such as lidocaine, flecainide, and quinidine). However, these conventional blockers show limitations because of the lack of selectivity, driving research toward more precise therapeutic directions. Additionally, this review evaluates gabapentin, cannabidiol, and calcium channel blockers with different mechanisms of action. These drugs modulate neuronal excitability from multiple perspectives, providing diverse options for symptom relief. This review also highlights advances in gene therapy for specific diseases, such as STK-001, which promotes effective splicing of the sodium channel voltage-gated type 1 alpha subunit ( SCN1A ) gene, and ETX101, which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors. These two agents provide targeted therapeutic solutions for Dravet syndrome. Furthermore, this review summarizes some innovative therapeutic agents in clinical trials, including PRAX-222 (for SCN2A gain-of-function mutation-related epilepsy), which has received Food and Drug Administration orphan drug designation, and the selective Nav1.6 inhibitor NBI-921352 (for SCN8A -related epilepsy). Collectively, this review comprehensively compares the advantages and disadvantages of conventional drugs and gene therapy and envisions future treatment strategies that integrate the strengths of both approaches, facilitating personalized precision medicine to provide more accurate and effective treatment options for patients with ion channel diseases.

Adult disease burden in patients with mucopolysaccharidosis type I H (Hurler syndrome): A comprehensive literature review with patient case analysis.