Swelling Scores Research Articles

Efficacy of medical compression stockings class I on the reduction of symptoms in patients with uncomplicated varicose veins.

Background: Aim of this study was to analyze the effect of medical compression stockings (MCS) class I (according to the German classification "RAL-GZ 387"; 18-21mmHg) on symptoms in patients with uncomplicated varicose veins (C2s-C4a). Patients and methods: We conducted a randomized (1:1), controlled, clinical trial enrolling patients with uncomplicated varicose veins (CEAP: C2s-C4a). The study consisted of a one-week baseline period and a four-week follow-up period with MCS treatment (compression class I, 18-21mmHg) in the intervention group and non-treatment in the control group. The frequency and severity of symptoms on the leg including heaviness, pain, swelling, throbbing and itching were measured every evening using an app-based measuring tool. The primary endpoint was the reduction of symptoms during compression therapy, measured by a symptom sum score over a period of 5 weeks ranging from 0 (no symptoms during the day) to 25 (symptoms all day). Results: Patients treated with MCS (n = 25) showed a significant improvement in the overall symptom sum score from 8.90 ± 4.26 at baseline to 6.37 ± 3.55 at follow-up (p = 0.004) whereas for patients in the control group without MCS (n = 25) the overall score remained unchanged (baseline: 7.46 ± 3.71; follow-up: 7.67 ± 4.74; p = 0.293). The intervention group reported significant improvements in symptom frequency scores for pain, leg swelling and feeling of leg heaviness (p ≤ 0.002). In the control group the score for pain significantly increased during the follow-up period. Leg itching was numerically more frequent in patients with MCS. Conclusion: This study indicates that medical compression stockings class I (according to the German classification "RAL-GZ 387"; 18-21 mmHg) significantly improve the frequency and severity of symptoms in patients with uncomplicated varicose veins (CEAP: C2s-C4a).

Modulation of Proinflammatory Cytokines by Parmotrema reticulatum Derived Dioxepine Derivative and Benzoic Methyl Ester in Adjuvant-Induced Arthritis.

The present investigation aims to study the therapeutic effect and to identify the lead molecules from lichen Parmotrema reticulatum (Pr) that can solve the complications associated with arthritis. Purification of Pr extract led to isolation of two lead molecules i.e. Compound A (a Dioxepine derivative) as 3-Hydroxy-9-hydroxymethyl-1,8-dimethyl-11-oxo-11H-dibenzo[b,e][1,4]dioxepine-4,7 dicarboxylic acid 7-methyl ester with molecular formula C19H16O9; molecular weight 388.34. Compound B as 3-Hydroxy-5-methoxy-4-methyl-benzoic acid (a Benzoic methyl ester) with molecular formula C9H10O4; molecular weight 182.2. In-silico investigation specific for inflammation revealed good binding affinity of both the compounds with the targeted proteins. Further continuous administration of Pr and novel compound A & B to CFA (Freund's complete adjuvant) induced arthritis rat revealed reduction in arthritis complication possibly by inhibiting the formation of edema. The variations in relative body weight along with paw swelling and arthritic scores were identified. Inhibition of expressions of RA markers like RF, CRP, TNF-𝛼, IL-1𝛽, IL-6, ALP, AST, ALT and LDH were observed there by inhibiting inflammation of synovial cavity and cartilage damage effectively. Hence from our results it is evident that Pr, Compound A & B has down regulated the inflammatory cytokines and can be a potential candidate to treat arthritis.

Sinulariolide Suppresses Inflammation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis and Mitigates Collagen-Induced Arthritis Symptoms in Mice.

Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by active polyarthritis, which leads to functional loss and joint deformities. Natural compounds derived from marine organisms are considered valuable immune-modulating agents. This study aimed to assess the anti-inflammatory effect of sinulariolide, a soft coral-derived compound, on RA fibroblast-like synoviocytes and its therapeutic efficacy against collagen-induced arthritis (CIA). To determine the effects of sinulariolide on tumor necrosis factor-alpha (TNF-α)-induced inflammation, MH7A cells pre-treated with 10 ng/mL TNF-α for 24h were treated with sinulariolide. The effect of sinulariolide on proinflammatory cytokine expressions at both the mRNA and protein levels in the MH7A cells was assessed using real-time-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Further, we analyzed the effect of sinulariolide on the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways using Western blotting and the TransAM NF-κB p65 kit. To comprehensively evaluate the potential application of sinulariolide in the treatment of inflammatory diseases, we used a well-established collagen-induced arthritis (CIA) mouse model. We examined the tissue sections of the ankle joints of the mice, assessed synovial hyperplasia, inflammatory cell infiltration, and cartilage damage, and used ELISA to analyze changes in cytokine expression in the hind paw tissues. MH7A cells treated with sinulariolide showed a notable reduction in the expression of proinflammatory cytokines, which could be due to decreased activation of the MAPK and NF-kB pathways. Additionally, sinulariolide-treated mice showed significantly reduced joint swelling and lower clinical arthritis scores than those in the normal and control groups. Significant reductions in synovial hyperplasia, inflammatory cell infiltration, and cartilage damage were observed in the tissue sections of the ankle joints of the mice treated with sinulariolide. Furthermore, the expression of inflammatory cytokines in the hind paw tissue of the mice treated with sinulariolide was significantly decreased. Sinulariolide inhibited the progression of inflammation in MH7A cells. Sinulariolide treatment significantly reduced clinical arthritis symptoms and histological inflammatory responses in mice with CIA. Sinulariolide may serve as a potential therapeutic agent for RA.

Safety and efficacy of intra-articular triamcinolone acetonide injection versus standard of care in patients with rheumatoid arthritis flare

Triamcinolone acetonide is a commonly used corticosteroid for rheumatoid arthritis (RA) flares, providing extended relief. However, there is limited data from controlled trials comparing the efficacy of intra-articular corticosteroid (IACS) injections to standard care, particularly with non-steroidal anti-inflammatory drugs (NSAIDs). This non-randomized, single-center, open-label study evaluated the safety and efficacy of IACS injections in RA patients experiencing knee joint flare-ups. A total of 64 patients were screened and 44 received IACS (triamcinolone acetonide) and 15 were included in the control group. Significant improvements were observed in the IACS group in pain, swelling, and morning stiffness at week 2, which were sustained through weeks 6 and 12. The swollen joint count significantly reduced by week 12, while the tender joint count showed improvement by week 2. Pain reduction was substantial, as indicated by significant decrease in visual analog scale scores for pain, swelling, and mobility. The disease activity score-28 improved significantly across all time points. In addition, the C-reactive protein level decreased significantly at week 2 and its decreasing trend continued until weeks 6 and 12. By week 2, all patients had ceased NSAID use. The study demonstrated the effectiveness of IACS in reducing RA flare severity, particularly in terms of pain, swelling, and functional impairment, with no major safety concerns reported.

Traditional craniotomy versus current minimally invasive surgery for spontaneous supratentorial intracerebral haemorrhage: A propensity-matched analysis.

Minimally invasive surgery (MIS) and craniotomy (CI) are the current treatments for spontaneous supratentorial cerebral haemorrhage (SSTICH). To compare the efficacy and safety of MIS and CI for the treatment of SSTICH. Clinical and imaging data of 557 consecutive patients with SSTICH who underwent MIS or CI between January 2017 and December 2022 were retrospectively analysed. The patients were divided into two subgroups: The MIS group and CI group. Propensity score matching was performed to minimise case selection bias. The primary outcome was a dichotomous prognostic (favourable or unfavourable) outcome based on the modified Rankin Scale (mRS) score at 3 months; an mRS score of 0-2 was considered favourable. In both conventional statistical and binary logistic regression analyses, the MIS group had a better outcome. The outcome of propensity score matching was unexpected (odds ratio: 0.582; 95%CI: 0.281-1.204; P = 0.144), which indicated that, after excluding the interference of each confounder, different surgical modalities were more effective, and there was no significant difference in their prognosis. Deciding between MIS and CI should be made based on the individual patient, considering the hematoma size, degree of midline shift, cerebral swelling, and preoperative Glasgow Coma Scale score.

Oroantral Fistula Reconstruction by Pedicled Buccal Pad of Fat adjuvant with Advancement Flap (Clinical Study)

Aim: As well as highlighting the role of buccal fat of pad in closure large defects by evaluating healing process through pain, swelling and wound healing scores. Material and Method: A prospective evaluation study was conducted among patients who underwent surgical closure to OAC in both Ear Nose and Throat Department with the Maxillofacial Department of Al-Salam Teaching Hospital in Mosul City of Nineveh Province. Data recorded includes demographical Information and clinical evaluations. Two operators measured the parameters. Pain and swelling assessment through the visual analogue scale (VAS) assess the level of pain on the third, seventh and day twenty following surgery. Wound Evaluation Scale used to evaluate closure of the oroantral communication without nasal regurgitation at 1st week (day 7) and 20th days post- surgery and measure the surgical success. Results: The highest age group are between (20-29 years) with percent (56.5). male show high incidence (56.5%) more than female (43.47). In regard to cause extraction followed by tumors are the common cause for oroantral fistula (56.5%, 17.39). Day three and seven reflect different ranges of pain with highest percent for severe pain in day three (65.21%) and reduced to slight pain (82.60%) in day seven. In regard to swelling, in day three most of cases show very severe swelling (73.91%). In day seven the cases represent sever swelling (78.26%). Twenty-one patients from total 23 show incomplete healing at day seven while two patients have uncertain healing. In day 20 just one patient shows incomplete healing process. Conclusion: Buccal pad of fat can be used safely as adjuvant to buccal advancement flap for closure and is efficient in management of OAC to avoid diminished soft tissue in different size cases. Pain, swelling scales can be used as assessment for healing process added to them soft tissue wound healing scale.

Manajemant Breast Engogerment Kompres Daun Kubis Dingin (Brassica Oleracea Var. Capitata) dan Breastcare terhadap Pembengkakan Payudara pada Ibu Nifas

Breast milk duct dams and swelling of the mammary glands are one of the lactation problems that occur after childbirth and during breastfeeding. Breast swelling occurs when the milk ducts do not drain completely and narrow. Milk thickens and the lumen of the milk ducts is blocked. From 3 to 6 days after birth until the milk is expelled normally, symptoms such as warmth, pain to the touch, tenderness, and swelling associated with breast swelling will appear. From 3 to 6 days after birth until the milk is expelled normally, symptoms such as warmth, pain to the touch, tenderness, and swelling associated with breast swelling will appear. The use of cabbage leaves for the treatment and prevention of breast swelling is very simple, the inside of cabbage leaves can be put in the freezer for approximately 20-30 minutes before the procedure. Place cold cabbage leaves inside your bra for 30 minutes and do it twice a day for 3 days. This study aims to determine the difference in effectiveness before and after cabbage leaves (Brassica Oleracea Var.Capitata) and Breast Care in Reducing Breast Swelling. This research is a quasi-experimental design research with one group pre and post design research methods. The population in this study was 34 postpartum mothers who experienced breast swelling on day 3 to day 14. The results of the Wilcoxon test found differences in breast swelling scores before and after applying cold cabbage leaf compresses and breastcare, so it can be concluded that there is a statistically significant average difference between breast swelling scores before and after treatment, where the mean after treatment decreased by 1.15 compared to the mean before treatment 2.79. This means that giving cold cabbage leaf compresses and breastcare can effectively reduce the problem of breast swelling in puerperal mothers. Applying cabbage leaf compresses (Brassica Oleracea var. Capitata) cold and Breast Care combined with very effective in reducing breast swelling in puerperal mothers.

Exploring the mechanism of Sendeng-4 against rheumacid arthritis through integrated serum pharmacochemistry, transcriptomics, and network pharmacology.

Mongolian medicine Sendeng-4 (SD-4) has demonstrated satisfactory clinical treatment outcomes for rheumatoid arthritis (RA); nevertheless, its bioactive components and the related mechanisms have not yet been clearly elucidated. To explore the bioactive chemical components of SD-4 in the treatment of RA and its possible mechanisms, an High Performance Liquid Chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously quantify the main components in SD-4, and ultraperformance LC-Q-Exactive-MS/MS (UPLC-Q-Exactive-MS/MS) was used to identify the phytochemicals absorbed in the serum. Then, using network pharmacology methods, these components were constructed into a compound-target network of RA to predict possible biological targets of SD-4 as well as potential signaling pathways. Transcriptomics analysis and molecular docking were used to validate the results of network pharmacology. Subsequently, we established a complete Freund's adjuvant-induced RA rat model and observed the anti-RA effects of SD-4 through assessments of foot swelling, ankle diameter, arthritis score, morphology, serum inflammatory factors, and histopathological analysis of synovial tissue. Specifically, reverse transcription-quantitative polymerase chain reaction, Western blot, and immunohistochemical analysis were used in animal experiments to validate the pathways of serum phytochemistry, network pharmacology, and transcriptomics. Tannic acid, gallic acid, corilagin, crocin I, gardenoside, ferulic acid, quercetin, limonin, rutin, chlorogenic acid, verbascoside, catechin, epicatechin, myricetin, and dihydromyricetin in SD-4 showed good linearity within their respective concentration ranges (r ≥ 0.9991); the average recovery rate was 93.77%-109.17% (relative standard deviation < 2%). A total of 37 compounds were identified in serum samples. Based on this, network pharmacology methods collected 739 genes related to these identified compounds in SD-4 and 3807 genes related to RA. Network pharmacology and transcriptomic analysis demonstrated that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway is the most relevant pathway affected by SD-4 in RA. In the experiments, SD-4 treatment reduced ankle swelling and arthritis scores in RA rats, improved symptoms, and reduced the production of inflammatory factors. Compared with the RA model group, SD-4 treatment significantly reduced the expression of PI3K-Akt pathway-related messenger RNA and proteins. In addition, immunohistochemical analysis confirmed these results. This study combined serum phytochemistry, network pharmacology, and transcriptomics to demonstrate that SD-4 can alleviate RA by regulating the PI3K-Akt signaling pathway. This research provides a theoretical basis for the clinical application of SD-4 and offers an effective strategy for the identification of bioactive substances in traditional Chinese medicine formulas and the study of their potential mechanisms.

Schisandrin B ameliorates adjuvant-induced arthritis in rats via modulation of inflammatory mediators, oxidative stress, and HIF-1α/VEGF pathway.

Schisandrin B (Sch B) has been shown to possess anti-inflammatory and antioxidant properties, however, its antirheumatoid arthritis properties and potential mechanism remain unexplored. This study evaluated the potential of Sch B in adjuvant-induced arthritic (AIA) rats. AIA was induced by injecting 0.1 ml of CFA into the paw of rats and the animals were administered with Sch B (50 mg/kg) for 28 days. The effects of Sch B were evaluated using arthritis severity, serum levels of oxido-inflammatory, and metabolic index parameters. Sch B eased arthritic symptoms by significantly reducing paw swelling and arthritic score and increased body weight gain. Moreover, Sch B alleviated the levels of oxido-inflammatory markers including interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, nuclear factor kappa B, transforming growth factor β1, inducible nitric oxide synthase and malonaldehyde, as well as increased the levels of superoxide dismutase, glutathione, and Nrf2. Sch B also remarkably restored the altered levels of triglyceride, aspartate aminotransferase, lactic acid, pyruvate, phosphoenolpyruvate carboxylase, glucose, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor. In addition, Sch B markedly alleviated p65 expression in the treated AIA rats. This study suggests that Sch B alleviated AIA by reducing oxidative stress, inflammation, and angiogenesis.

Evaluation of minimally invasive esthetic crown lengthening using an open flap versus flapless surgical approach: A randomized controlled clinical trial.

Esthetic crown lengthening (ECL) is commonly advocated to treat patients with altered passive eruption (APE). Since the introduction of the minimally invasive surgical concept, a limited number of studies have investigated this technique in a standardized manner, with further studies required to verify the validity and predictability of the minimally invasive FL-technique. The current randomized trial compares a minimally invasive (ECL), using piezosurgery with flapless-approach (FL), versus an open-flap (OF) approach in the management of patients with APE Type 1B. Twenty-four patients diagnosed with APE Type 1B were randomly assigned into test (FL) with tunneling approach or control (OF) group with minimally invasive flap reflection (n = 12/group). Postoperative pain was assessed during the first 48 h. Gingival margin (GM) level relative to a custom-made stent (rGM) and patient satisfaction were assessed preoperative, immediately after surgery, at 3 and 6 months postsurgically. Postoperative swelling was reported for the first week postsurgically. Plaque index (PI), bleeding on probing (BoP), clinical attachment level (CAL), pocket depth (PD) and pink esthetic score (PES), were evaluated at baseline and 6 months. Linear regression analysis was conducted for pain. OF-group reported significantly higher pain and swelling scores than FL-group during the first 48 h (p < 0.05). FL-group showed no significant differences regarding rGM between 3 and 6 months, in contrast to OF-group, where a significant decrease in rGM was notable (p < 0.05). No significant differences in PI, BoP, CAL, PD, PES, and patient satisfaction scores were evident between groups (p > 0.05). Regression analysis demonstrated that treatment and gender were significant predictors for pain (p < 0.05). Within the current study's limitations, piezo-surgical ECL with FL-approach presented significantly lower postoperative pain, swelling, and early GM stability compared to OF-approach. Piezosurgical ECL with a FL-approach can be considered a predictable technique with advantages over the OF-approach in the management of patients with APE Type1B.

The effect of autologous demineralized dentin matrix on postoperative complications and wound healing following lower third molar surgery: A split-mouth randomized clinical trial

Background/purposeAutologous dentin materials are among the most promising bone substitutes for preventing osseous defects on the distal side of the lower second molar. This study aimed to investigate the effects of autologous demineralized dentin matrix on postoperative complications and wound healing after lower third molar surgery. Materials and methodsThirteen patients with bilateral symmetrical lower third molars participated in this split-mouth randomized clinical trial. After removal surgery, one socket of the lower third molar was grafted with dentin material (demineralized dentin matrix side), and a piece of collagen sponge was used for the tooth socket of the remaining side (control side). The upper third molar on the same lateral side was extracted immediately before lower third molar surgery and used to create a demineralized dentin matrix according to the manufacturer's protocol (KometaBio). After lower third molar surgery, pain, swelling, trismus, and Inflammatory Proliferative Remodeling Scale scores were used to evaluate postoperative complications and wound healing. ResultsPain, swelling, and trismus of the demineralized dentin matrix and control sides were not significantly different at any assessment time (P > 0.05). The wound-healing scores of the demineralized dentin matrix side were better than those of the control side; however, the differences were only significant at 7th and 30th days (P < 0.05). ConclusionGrafting autologous demineralized dentin matrix into the tooth socket did not increase the postoperative complications after lower third molar surgery. However, wound healing on the graft side was comparatively better than that on the control side. Clinicaltrials.gov identifierNCT06073639, date 10 October, 2023. This is a retrospectively registered trial.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10mg dexamethasone intravenously and the PI group received periarticular injection of 10mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Role of nutritional support in nursing practice for improving surgical site wound healing in patients post-surgery with risk of pressure ulcers.

To explore the role of nutritional support in nursing practice on postoperative surgical site wound healing in patients undergoing surgery at risk for pressure ulcers. This study adopted a retrospective experimental design and included a total of 60 patients at risk of pressure ulcers, divided into a nutritional support group and a control group, with 30 people in each group. The nutritional support group implemented specific nutritional support measures after surgery, while the control group received standard postoperative care. Outcome measures included redness and swelling scores, edema scores, anxiety assessments, pain scores, bleeding volume, recovery time and incidence of pressure ulcers. The result indicates that patients who received nutritional support exhibited lower postoperative wound redness and swelling scores compared to the control group (3.11 ± 0.45 vs. 4.85 ± 0.74, p < 0.05). Additionally, the nutritional support group showed significantly lower edema scores (2.75 ± 0.37 vs. 3.53 ± 0.62, p < 0.05). Anxiety levels, as measured by the anxiety assessment scale (SAS), were also lower in the nutritional support group (6.52 ± 1.19 vs. 7.60 ± 1.62, p < 0.05). Moreover, the average healing time was shorter for the nutritional support group (7.27 ± 1.36 days) compared to the control group (9.71 ± 1.84 days, p < 0.05). Postoperative pain scores were lower in the nutritional support group (4.13 ± 0.72 vs. 5.43 ± 0.62, p < 0.05), and patient satisfaction scores were higher (9.42 ± 0.76 vs. 7.25 ± 0.81, p < 0.05). Nutritional support has a positive effect on postoperative wound healing at surgical sites in patients at risk of pressure ulcers in nursing practice. It can significantly reduce redness, swelling, edema, anxiety, and pain scores, reduce bleeding, shorten recovery time, and reduce pressure ulcers. incidence rate.

Clinical value of rehabilitation nursing after internal fixation of distal radius fractures.

To evaluate the clinical value of rehabilitation nursing following internal fixation of distal radius fractures (DRFs). This retrospective study analyzed the medical records of 114 patients who underwent internal fixation for DRFs between July 2019 and May 2023. Among them, 54 patients received routine nursing care (control group) and 60 patients received rehabilitation nursing (observation group). Comparative analyses were conducted on postoperative pain (Visual Analogue Scale [VAS]), swelling, rehabilitation indicators (healing time, time to regain limb mobility, and hospital stays), wrist joint functional recovery (grip strength, Gartland-Werley Scale, rate of excellent and good reduction), quality of life (Short-Form 36 [SF-36]), adverse emotions (Self-Rating Depression Scale [SDS] and Self-Rating Anxiety Scale [SAS]), and nursing satisfaction. The observation group exhibited a significant stepwise decrease in VAS and swelling scores on postoperative days 3 and 7 compared to preoperative levels (all P<0.05), and these scores were lower than those of the control group (all P<0.05). The observation group also showed significantly shorter healing time, faster recovery of limb mobility, and reduced hospital stays (all P<0.05). Additionally, patients in the observation group demonstrated higher grip strength, a greater rate of excellent and good reduction, and significantly lower Gartland-Werley, SDS, and SAS scores compared to the control group (all P<0.05). Higher SF-36 scores and greater nursing satisfaction were also observed in the observation group (both P<0.05). Rehabilitation nursing after internal fixation of DRFs has significant clinical value, evidenced by substantial relief of postoperative pain and swelling, reduction in adverse emotions, enhanced rehabilitation, improved wrist joint function, and higher quality of life and nursing satisfaction.

Xinfeng Capsule Inhibits Pyroptosis and Ameliorates Myocardial Injury in Rats with Adjuvant Arthritis via the GAS5/miR-21/TLR4 Axis.

This study probed the mechanism of action of Xinfeng Capsule (XFC) in myocardial injury in rats with adjuvant arthritis (AA) via the growth arrest-specific transcript 5 (GAS5)/microRNA-21 (miR-21)/Toll-like receptor 4 (TLR4) axis. Rats were injected with Freund's complete adjuvant to establish a rat model of AA. Then, some modeled rats were given normal saline or drugs only, and some modeled rats were injected with adeno-associated viruses or necrosulfonamide (NSA; a pyroptosis inhibitor) before drug administration. Toe swelling and arthritis index (AI) were calculated. Pathological and morphological changes in synovial and myocardial tissues were analyzed with hematoxylin-eosin staining, and pyroptotic vesicles and the ultrastructural changes of myocardial tissues were observed with transmission electron microscopy. The serum levels of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were detected, and lactate dehydrogenase (LDH) release was measured in myocardial tissues, accompanied by the examination of GAS5, miR-21, TLR4, nuclear factor-kB (NF-κB) p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and Gasdermin D (GSDMD) expression in myocardial tissues. After AA modeling, rats presented with significantly increased toe swelling and AI scores, synovial and myocardial tissue damage, elevated pyroptotic vesicles, and markedly enhanced serum levels of IL-1β, IL-18, IL-6, and TNF-α, accompanied by significantly diminished GAS5 expression, substantially augmented miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression, greatly increased LDH release in myocardial tissues. XFC treatment significantly declined toe swelling, AI scores, synovial and myocardial tissue damage, and the serum levels of IL-1β, IL-18, IL-6, and TNF-α in AA rats. Additionally, XFC treatment markedly elevated GAS5 expression and substantially lowered LDH release and miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression in myocardial tissues of AA rats. Moreover, the above effects of XFC in AA rats were further promoted by GAS5 overexpression or NSA treatment. XFC alleviated myocardial injury in AA rats by regulating the GAS5/miR-21/TLR4 axis and inhibiting pyroptosis and pro-inflammatory cytokine secretion.

Mechanism of Rhodiola rosea-Euonymus alatus drug pair against rheumatoid arthritis: Network pharmacology and experimental validation.

The present study aimed to explore the potential components and mechanisms of Rhodiola rosea-Euonymus alatus drug pair (TY) that ameliorate rheumatoid arthritis (RA). The main active components, core targets, and important pathways of TY against RA were predicted by network pharmacology analysis. The binding activity between the main active components and the core targets was verified by the molecular docking technique. Collagen-induced arthritis (CIA) rat model and tumor necrosis factor (TNF)-α-induced fibroblast-like synovial cells in human RA (HFLS-RA) model were established, respectively. The core targets were verified by cell counting kit-8 assay, hematoxylin eosin, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis, and the therapeutic effect of TY was evaluated. A total of 18 possible components and 34 core targets were obtained by network pharmacology, among which inflammatory response, phosphatidylinositide 3-kinases (PI3K)-AKT and MAPK pathways were involved in the therapeutic effect of TY on RA. The results of molecular docking showed that kaempferol and quercetin had high binding affinity to interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)9, and TNF-α. In vivo and in vitro experiments showed that TY dose-dependently inhibited the proliferation of HFLS-RA cells induced by TNF-α, and significantly reduced the paw swelling and arthritis scores in CIA rats. At the same time, TY inhibited the production of inflammatory factors in CIA rat serum and TNF-α-induced HFLS-RA cells. It also decreased the expression of PI3K, phospho-protein kinase B, MMP1, MMP3, MMP9, and increased the protein and mRNA levels of tissue inhibitors of MMPs (TIMP)1 in synovial tissue. TY can inhibit the PI3K/AKT signaling pathway and regulate the balance between MMPs and TIMP, thus playing a therapeutic role in RA.

Appraisal of anti-arthritic potential of Coronopus didymus (L.) Sm. aqueous extract and its safety study in Wistar rats.

The current study aimed to find out the anti-arthritic activity and safety study of Coronopus didymus aqueous extract (CDAE) as well as its chemical characterization by HPLC-DAD. Safety study including acute and subacute toxicity studies of the plant aqueous extract was also performed. In complete Freund's adjuvant-induced arthritic model (CFA), 0.15ml CFA was injected in the left hind paw at day 1 in all rats except normal rats. Treatment with CDAE at 200, 400, and 800mg/kg and methotrexate (1mg/kg) was administered at day 8 and continued till 28th day using oral gavage. The CDAE considerably (p < 0.05) reduced the paw swelling and arthritic score, and reinstated the body weight and blood parameters. The CDAE considerably modulated superoxide dismutase, catalase, reduced glutathione, and malondialdehyde level in liver homogenate in contrast to disease control. The CDAE at 400mg/kg considerably reduced IL-6, IL -1β, COX-2, and NF-ĸβ, whereas elevated IL-10, IL-4, and I-kappa β as equated to disease and standard groups. The LD50 of CDAE > 2000mg/kg. In subacute toxicity study, CDAE at 200-800mg/kg did not exhibit clinical signs of toxicity, mortality, hematological, biochemical, and histological alteration in the liver heart, kidney, and lungs in contrast to the normal group. It was concluded that the presence of delphinidine-3-glucoside, diosmetin, 3-feruloyl-4,5-dicaffeoyl quinic acid, and gallic acid in CDAE might be accountable for its anti-arthritic activity and safe use for a long period.

Identification of HHT-9041P1: A novel potent and selective JAK1 inhibitor in a rat model of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic disease associated with long-term disability and premature mortality. If left untreated, it can seriously affect patients’ quality of life. The JAK-STAT signal transduction process is known to affect the occurrence and development of RA, and small molecule JAK inhibitors, such as tofacitinib, have been identified as treatments for RA. However, tofacitinib is a non-selective JAK inhibitor that was found to be associated with dose-limiting tolerability and safety issues, such as anemia in phase 2 dose-ranging studies. Therefore, we developed a selective JAK1 inhibitor, HHT-9041P1, to overcome target-related adverse reactions. We used enzyme and cytokine potency assays in vitro as well as the collagen-induced arthritis (CIA) model in vivo to explore the efficacy and mechanism. In vitro, HHT-9041P1 was diluted (0.017 nM–1 mM) in DMSO) and mixed with JAK1, JAK2, JAK3 or TYK2 kinases for use in the respective assays for inhibitory activity and selectivity evaluation. Fresh human PBMCs were activated and incubated with 100 ng/mL cytokine IL-6 or 20 ng/mL GM-CSF for use in the investigation of the immune mechanism. In vivo, HHT-9041P1 (1 mg/kg, 3 mg/kg and 10 mg/kg) was administered by oral gavage twice daily to CIA model Lewis rats from Day 8 to Day 29 for paw swelling and arthritis score evaluation. At the end of the experiment, the rats were sacrificed before collection of the hind ankle joint, spleen and blood for analysis of inflammation, arthritis phenotypes, inflammatory cytokine expression and Th1 cell proportions. As expected, HHT-9041P1 showed 10-fold greater selectivity for JAK1 over JAK2, and 23-fold greater selectivity over JAK3 in cellular assays. The high selectivity of HHT-9041P1 was also validated by in vivo safety studies. HHT-9041P1 demonstrated significant efficacy in a rat model of collagen-induced arthritis (CIA) and was associated with reduced helper T Cell 1 (Th1) cell differentiation. HHT-9041P1 also exhibited excellent pharmacokinetics properties. Thus, HHT-9041P1 was identified as a candidate for clinical development with many options for the treatment of RA.

Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury transforming growth factor beta1 signaling and metabolic reprogramming.

To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor beta1 (TGF-β1)/Smads signaling pathway. One hundred rats were treated with saline [normal control (NC) group] or complete Freund's adjuvant (CFA) by right plantar injection for the RA model group, and the latter were randomly divided into 4 groups. Tripterygium wilfordii polyglycoside tablets (, TPT) have anti-inflammatory and are widely used in the clinical treatment of RA, therefore serving as a positive control group. Three days post injection rats were given TPT tablet (TPT group), acupuncture therapy (APT group), and moxibustion treatment (MOX group) for 15 consecutive days, while NC group and model group were equally grasped and fixed and received normal saline. Rat joint swelling scores and arthritis index (AI) were evaluated in each group before the CFA challenge, therapy and after receiving therapy. Myocardial ultrastructure was observed by electron microscope. Enzyme-linked immunosorbent assay was used to detect cardiac troponin I (cTnI) levels in rat myocardial tissue. Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-β signaling molecules including TGF-β1, Smad2, Smad3, Smad4, and Smad7. Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer. Compared with model group, RA model rats receiving TPT, acupuncture, or moxibustion therapy all showed reduced joint swelling scores and AI (all P < 0.01) and improved myocardial damage, whereas rats treated with moxibustion were found to be more marked. Consistently, the expressions of cTnI, TGF-β1, Smad2, Smad3, and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT, APT and MOX group when compared with model group, while the levels of Smad7 showed the opposite result (all P < 0.01). Moreover, the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate, dihydroxyacetone phosphate, arachidonic acid, etc was defined and implicated in amino acid, glucose, and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis. Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions. The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.

Curcumin Co-Encapsulation Potentiates Anti-Arthritic Efficacy of Meloxicam Biodegradable Nanoparticles in Adjuvant-Induced Arthritis Animal Model.

This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation efficiency (%), compound-polymer interactions (FT-IR analysis), and surface morphology (SEM imaging). In vivo, Complete Freund's adjuvant-induced arthritic rats were intraperitoneally (i.p.) administered with curcumin, meloxicam, curcumin plus meloxicam, nCur, nMlx, and nCur/Mlx for 28 consecutive days. Results showed that nCur, nMlx, and nCur/Mlx significantly (p ≤ 0.05) reduced paw swelling and arthritic score, restored body weight and the immune organ index (thymus and spleen), as well as attenuated serum inflammatory markers (RF, CRP, and PGE2) and oxidative stress parameters (MDA, SOD, and CAT) in adjuvant-induced arthritic rats compared to free compounds. In addition, mono- and dual-compound-loaded nanoparticles significantly (p ≤ 0.05) down-regulated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), up-regulated anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ), and modulated OPG and RANKL expressions in paw tissue. The aforementioned results were further confirmed through radiological and histopathological examinations. Furthermore, the anti-arthritic effect of nCur/Mlx was notably (p ≤ 0.05) enhanced compared to nCur or nMlx alone. In conclusion, the co-nanoencapsulation of curcumin could potentiate the anti-arthritic activity of meloxicam and could provide a novel therapeutic approach for the formulation of nanocarrier pharmaceutical products for the management of arthritis.