Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund\'s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

Forceps, clamps, and haemostats are essential surgical tools required for all surgical interventions. While they are widely used to grasp, hold, and manipulate soft tissue, their metallic rigid structure may cause tissue damage due to the potential risk of applying excessive gripping forces. Soft pneumatic surgical grippers fabricated by silicone elastomeric materials with low Young\'s modulus may offer a promising solution to minimize this unintentional damage due to their inherent excellent compliance and compressibility. The goal of this work is to evaluate and compare the grip-induced nerve damage caused by the soft pneumatic elastomeric gripper and conventional haemostats during surgical manipulation. Twenty-four Wistar rats (male, seven weeks) are subjected to sciatic nerve compression (right hind limb) using the soft pneumatic elastomer gripper and haemostats. A histopathological analysis is conducted at different time-points (Day 0, Day 3, Day 7 and Day 13) after the nerve compression to examine the morphological tissue changes between the rats in the \'soft gripper\' group and the \'haemostats\' group. A free walking analysis is also performed to examine the walking function of the rats after recovery from different time points. Comparing the rigid haemostats and soft gripper groups, there is a visible difference in the degree of axonal vacuolar degeneration between the groups, which could suggest the presence of substantial nerve damage in the \'haemostats\' group. The rats in the haemostats group exhibited reduced right hind paw pressure and paw size after the nerve compression. It shows that the rats tend not to exert more force on the affected right hind limb in the haemostats group compared to the soft gripper group. In addition, the stance duration was reduced in the injured right hind limb compared to the normal left hind limb in the haemostats group. These observations show that the soft pneumatic surgical gripper made of silicone elastomeric materials might reduce the severity of grip-induced damage by providing a safe compliant grip compared to the conventional haemostats. The soft pneumatic elastomer gripper could complement the current surgical gripping tool in delicate tissue manipulation.

Outer membrane vesicles (OMVs) of Neisseria meningitidis contain important antigens to trigger an immune response against meningococci and have been studied as vaccines compounds. The immune response to a vaccine may be affected by its constitution and route of administration. Therefore, Swiss mice were immunized by different routes with OMVs of N. meningitidis B with dimethyl dioctadecyl ammonium bromide in bilayer fragments (DDA-BF) or aluminum hydroxide (AH) as adjuvants. The adjuvants and different routes were compared regarding the immune responses by ELISA, western blot, delayed type hypersensitivity (DTH) and histopathologic analysis. The antigenic preparation generated humoral and cellular immune responses. In quantitative analyzes, in general, AH was superior to DDA-BF. However, analysis such as IgG avidity index, bactericidal activity and immunoblot, revealed no important differences regarding the adjuvant or route of immunization. Regarding the parameters tested, it was not possible to define a superiority between the adjuvants and routes of immunization proposed by this study.

Sarcopenia is characterized as aging-related weakness and atrophy, which decreases the diaphragm force generating capacity leading to a decrease of expulsive non-ventilatory motor behaviors, which are critical for airway clearance. Thus, this study aimed to analyze the histopathology of the diaphragm in postmortem samples. Thirty individuals were included. Diaphragm samples were stained with hematoxylin and eosin for histopathological analysis. Picrosirius stain was used to highlight the collagen fibers. We observed a positive association between advancing age and histopathological findings in the diaphragm structure. We suggest that age is a key factor in increasing diaphragm muscle histopathology. However, further clinicopathological studies are needed to confirm our findings.

OBJECTIVE: Smoking is a major risk factor for several cardiovascular and pulmonary diseases, and it has also been associated with the loss of skeletal muscle mass and strength leading to sarcopenia. The aim of this is study is to analyze the effects of cigarette smoking on the diaphragm muscle histopathology of postmortem samples from patients without respiratory diseases.
METHODS: Diaphragm samples were stained with hematoxylin and eosin for histopathological analysis. Picrosirius stain was used to highlight the collagen fibers.
RESULTS: Cigarette smokers had an increase of histopathological alterations as abnormal cytoplasm, abnormal fiber size and shape, and central nucleus. Additionally, smokers had an increase of collagen fibers on diaphragm muscle.
CONCLUSIONS: Smoking may influence in a negatively fashion the diaphragm musculature.

BACKGROUND: Modified Simiaowan (MSW) is frequently prescribed in traditional Chinese medicine and is famous for its efficiency in treating gouty diseases. We investigated the effectiveness of MSW as an anti-gouty inflammation medicine and its mechanism of action in monosodium urate (MSU) crystal-induced gouty rat in vivo and human umbilical vein endothelial cells (HUVECs) in vitro.
METHODS: Rats were orally administered with the water extract of MSW (2.5, 5.0, and 10 g/kg body weight), and indomethacin (12.5 mg/kg body weight) was given as a positive control. An intra-articular injection of 0.1 ml (10 mg) of MSU crystals was used to generate the gout model to assess paw volume at 1, 3, and 5h after MSU crystal injection and to analyze the histopathology of joint synovial tissues in the control and MSU crystal-treated rats at the end of the experiment. The HUVEC viability, expression levels of endothelial cell intercellular adhesion molecule-1 (ICAM-1), and apoptotic HUVECs were assessed in MSU crystal-induced HUVECs treated with (75 μg/ml to 300 μg/ml) MSW and (20 μg/ml) indomethacin by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, reverse transcriptase PCR, and acridine orange/ethidium bromide staining, respectively.
RESULTS: MSW could significantly prevent the paw swelling and neutrophil infiltration induced by intra-articular MSU injection in rats. MSW also showed potent analgesic effects at (5.0, 10, and 20 g/kg body weight) in acetic acid-induced mice depending on the dosage. Moreover, MSW could significantly increase HUVEC viability, attenuate the expression of ICAM-1, and prevent apoptosis of HUVECs in MSU-induced HUVECs.
CONCLUSIONS: These results provide evidence for the anti-inflammatory effect of MSW by preventing neutrophil infiltration and apoptosis of HUVECs. These mechanisms of action of MSW are similar to that by indomethacin. Therefore, the results support the effectiveness of MSW in treating gouty diseases.