Objective: To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis (KOA) model. Methods: Rabbits (n = 18) were randomly divided into control, KOA, and KOA + acupotomy (Apo) groups (n = 6). The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks. After modeling, the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa tendons around the knee. The behavior of all animals was recorded, rectus femoris tissue was obtained, and histomorphological changes were observed using Masson staining and transmission electron microscopy. The expression of transforming growth factor-β1 (TGF-β1), Smad 3, Smad 7, fibrillar collagen types I (Col-I) and III (Col-III) was detected using Western blot and real-time polymerase chain reaction (RT-PCR). Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris, compared with the KOA group (P = .034). Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA, thus preventing skeletal muscle fibrosis. Western blot and RT-PCR analysis revealed that in the Apo group, Col-I, and Col-III protein levels were significantly lower than those in the KOA group (both P < .01), same as Col-I and Col-III mRNA levels (P = .0031; P = .0046). Compared with the KOA group, the protein levels of TGF-β1 and Smad 3 were significantly reduced (both P < .01), as were the mRNA levels of TGF-β1 and Smad 3 (P = .0007; P = .0011). Conversely, the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group (P < .01; P = .0271). Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

Innate and adaptive immune responses initiated by infection depend on recognition and control of pathogens by macrophages,dendritic cells,T cells and so on.Notch signaling pathway is a highly conserved pathway,which is activated by interac-tion of receptors and ligands,thus coordinating important life processes of cells.At present,it has been confirmed that Notch signaling pathway is involved in development,differentiation,maturation and activation of many kinds of immune cells,and plays an important role in infectious diseases.In this review,we mainly focus on the role of Notch signaling pathway in immune regulation during different pathogens infection and its interaction with other signaling pathways.Additionally,therapeutic methods and challenges of developing Notch signaling as a target in infectious diseases are also discussed.

Objective To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization(MR)approach.Meth-ods Summary data for exposure factors and outcome were obtained from different genome-wide associ-ation studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted(IVW)method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results.Results The random-effects model of IVW analysis showed that heel bone mineral density(OR=0.986;95％CI,0.974 to 0.998;P=0.023)as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density(OR=1.031;95％CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density(OR=1.014;95％CI,0.973 to 1.057;P=0.505),and forearm bone mineral density(OR=1.011;95％CI,0.935 to 1.094;P=0.775)as outcome datasets showed no causal effect with bron-chial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results.Conclusion MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone miner-al density in patients with bronchial asthma to timely detect and intervene osteoporosis.

Objective To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization(MR)approach.Meth-ods Summary data for exposure factors and outcome were obtained from different genome-wide associ-ation studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted(IVW)method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results.Results The random-effects model of IVW analysis showed that heel bone mineral density(OR=0.986;95％CI,0.974 to 0.998;P=0.023)as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density(OR=1.031;95％CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density(OR=1.014;95％CI,0.973 to 1.057;P=0.505),and forearm bone mineral density(OR=1.011;95％CI,0.935 to 1.094;P=0.775)as outcome datasets showed no causal effect with bron-chial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results.Conclusion MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone miner-al density in patients with bronchial asthma to timely detect and intervene osteoporosis.

Macrophage as a crucial component of innate immunity, plays an important role in inflammation and infection immunity. Notch signal pathway is a highly conserved pathway, which regulates cellular fate and participates in numerous pathological processes. At present, a lot of literature has confirmed the role of Notch signaling in regulating the differentiation, activation and metabolism of macrophage during inflammation and infection. This review focuses on how Notch signaling promotes macrophage pro-inflammatory and anti-infective immune function in different inflammatory and infectious diseases. In this regulation, Notch signaling interact with TLR signaling in macrophages or inflammatory-related cytokines including IL-6, IL-12, and TNF-α. Additionally, the potential application and challenges of Notch signaling as a therapeutic target against inflammation and infectious diseases are also discussed.
Humans ; Signal Transduction ; Macrophages ; Cytokines/metabolism* ; Inflammation/metabolism* ; Communicable Diseases ; Receptors, Notch/metabolism*