NLRP3 Inflammasomes: Dual Function in Infectious Diseases.

The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been the most distinctive polymer protein complex. After recognizing the endogenous and exogenous danger signals, NLRP3 can cause inflammation by pyroptosis and secretion of mature, bioactive forms of IL-1ß and IL-18. The NLRP3 inflammasome is essential in the genesis and progression of infectious illnesses. Herein, we provide a comprehensive review of the NLRP3 inflammasome in infectious diseases, focusing on its two-sided effects. As an essential part of host defense with a protective impact, abnormal NLRP3 inflammasome activation, however, result in a systemic high inflammatory response, leading to subsequent damage. In addition, scientific evidence of small molecules, biologics, and phytochemicals acting on the NLRP3 inflammasome has been reviewed. We believe that the NLRP3 inflammasome helps us understand the pathological mechanism of different stages of infectious diseases and that inhibitors targeting the NLRP3 inflammasome will become a new and valuable research direction for the treatment of infectious diseases.

Histone deacetylases and inhibitors in diabetes mellitus and its complications.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, with its prevalence linked to both genetic predisposition and environmental factors. Epigenetic modifications, particularly through histone deacetylases (HDACs), have been recognized for their significant influence on DM pathogenesis. This review focuses on the classification of HDACs, their role in DM and its complications, and the potential therapeutic applications of HDAC inhibitors. HDACs, which modulate gene expression without altering DNA sequences, are categorized into four classes with distinct functions and tissue specificity. HDAC inhibitors (HDACi) have shown efficacy in various diseases, including DM, by targeting these enzymes. The review highlights how HDACs regulate ß-cell function, insulin sensitivity, and hepatic gluconeogenesis in DM, as well as their impact on diabetic cardiomyopathy, nephropathy, and retinopathy. Finally, we suggest that targeted histone modification is expected to become a key method for the treatment of diabetes and its complications. The study of HDACi offers insights into new treatment strategies for DM and its associated complications.

Association between oral microbiome and five types of respiratory infections: a two-sample Mendelian randomization study in east Asian population.

Objective: To explore the causal relationship between the oral microbiome and specific respiratory infections including tonsillitis, chronic sinusitis, bronchiectasis, bronchitis, and pneumonia, assessing the impact of genetic variations associated with the oral microbiome. Methods: Mendelian randomization was used to analyze genetic variations, leveraging data from genome-wide association studies in an East Asian cohort to identify connections between specific oral microbiota and respiratory infections. Results: Our analysis revealed that Prevotella, Streptococcus, Fusobacterium, Pauljensenia, and Capnocytophaga play crucial roles in influencing respiratory infections. Prevotella is associated with both promoting bronchitis and inhibiting pneumonia and tonsillitis, with a mixed effect on chronic sinusitis. Streptococcus and Fusobacterium show varied impacts on respiratory diseases, with Fusobacterium promoting chronic sinusitis, bronchiectasis, and bronchitis. Conversely, Pauljensenia and Capnocytophaga are linked to reduced bronchitis and tonsillitis, and inhibited pneumonia and bronchitis, respectively. Discussion: These findings underscore the significant impact of the oral microbiome on respiratory health, suggesting potential strategies for disease prevention and management through microbiome targeting. The study highlights the complexity of microbial influences on respiratory infections and the importance of further research to elucidate these relationships.

Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia.

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in "Synopsis of Golden Chamber" (Han Dynasty in the 3rd century) and the Zhizhu pill in "Differentiation on Endogenous" in Jin Dynasty (1,115-1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD). Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD. Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored. Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats. Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.

[Reconstruction of soft tissue defects at nose, lip, and cheek with facial artery perforator flaps].

OBJECTIVE: To investigate the therapeutic effect of facial artery perforator flap for the soft tissue defects at nose, lip and cheek. METHODS: The facial artery perforator adjacent to the defect was identified by Doppler ultrasonography. The perforator flap was designed according to the defect location, size and shape. The subcutaneous tissue around the perforator was kept as much as possible to protect the venous drainage. RESULTS: From Oct. 2012 to Oct.2013, 26 cases were treated with facial artery perforator flaps, with 9 cases of nasal defects, 10 cases of lip defects and 7 cases of buccal defects. The defects size ranged from 1.5 cm x 2.0 cm to 3.0 cm x 3.0 cm and the flaps size ranged from 2.0 cm x 2.5 cm to 3.5 cm x 3. 5 cm. Superficial necrosis(3mm in width) happened at the end of one flap. All the other 25 flaps survived completely. 16 cases were followed up for 3 months to 2 years with no relapse and satisfactory cosmetic and functional results were achieved. CONCLUSIONS: Both cosmetic and functional effect can be achieved with facial artery perforator flap for defects at nose, lip and cheek.