Distinctive Neurophysiological Signatures of Analgesia after Inflammatory Pain in the ACC of Freely Moving Mice.

Preclinical assessments of pain have often relied upon behavioral measurements and anesthetized neurophysiological recordings. Current technologies enabling large-scale neural recordings, however, have the potential to unveil quantifiable pain signals in conscious animals for preclinical studies. Although pain processing is distributed across many brain regions, the anterior cingulate cortex (ACC) is of particular interest in isolating these signals given its suggested role in the affective ("unpleasant") component of pain. Here, we explored the utility of the ACC toward preclinical pain research using head-mounted miniaturized microscopes to record calcium transients in freely moving male mice expressing genetically encoded calcium indicator 6f (GCaMP6f) under the Thy1 promoter. We verified the expression of GCaMP6f in excitatory neurons and found no intrinsic behavioral differences in this model. Using a multimodal stimulation paradigm across naive, pain, and analgesic conditions, we found that while ACC population activity roughly scaled with stimulus intensity, single-cell representations were highly flexible. We found only low-magnitude increases in population activity after complete Freund's adjuvant (CFA) and insufficient evidence for the existence of a robust nociceptive ensemble in the ACC. However, we found a temporal sharpening of response durations and generalized increases in pairwise neural correlations in the presence of the mechanistically distinct analgesics gabapentin or ibuprofen after (but not before) CFA-induced inflammatory pain. This increase was not explainable by changes in locomotion alone. Taken together, these results highlight challenges in isolating distinct pain signals among flexible representations in the ACC but suggest a neurophysiological hallmark of analgesia after pain that generalizes to at least two analgesics.

In vivo evaluation of efficacy and safety of Coagulansin-A in treating arthritis.

The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model.

Prognostic significance of the CFA ratio for newly diagnosed acute myeloid leukemia: A multicenter retrospective study.

The CFA ratio, calculated using pretreatment C-reactive protein (CRP), fibrinogen, and albumin levels (CRP × fibrinogen/albumin), was previously reported to be a significant prognostic factor for acute myeloid leukemia (AML). This multicenter retrospective study evaluated the prognostic value of the CFA ratio in 328 adult patients with newly diagnosed AML from April 2000 to March 2018. The median age was 49.5 years (range, 15-75 years), and 60.7% of the population were males. According to the European LeukemiaNet (ELN) risk classification, 67 patients (20.4%) were in the favorable-risk group, 197 patients (60.1%) in the intermediate-risk group, and 58 patients (17.7%) in the adverse-risk group. The median CFA ratio was 1.07 (0-67.69). Based on the calculated cutoff CFA ratio of 1.44, the cohort included 176 and 152 patients with low and high CFA ratios, respectively. At a median follow-up of 91.2 months, the 7-year overall survival (OS) and disease-free survival (DFS) rates were 51.2% and 48.6%, respectively, in the overall cohort. The 7-year OS rates were 61.7% and 39.0% in the low and high CFA ratio groups, respectively (p < 0.001). The 7-year DFS rates were 58.1% and 37.0% in the low and high CFA ratio groups, respectively (p = 0.004). In univariate analysis, age ≥50 years, male sex, ELN risk class, and comorbidities were associated with poor OS. Age, ELN risk class, comorbidities, and high CFA ratio were associated with poor OS in multivariate analysis. Subgroup analysis revealed that the CFA ratio was significant in the intermediate and adverse ELN risk classes. These findings indicate the prognostic significance of the CFA ratio in AML.

Assessing the properties of patient-specific treatment effect estimates from causal forest algorithms under essential heterogeneity.

BACKGROUND: Treatment variation from observational data has been used to estimate patient-specific treatment effects. Causal Forest Algorithms (CFAs) developed for this task have unknown properties when treatment effect heterogeneity from unmeasured patient factors influences treatment choice - essential heterogeneity. METHODS: We simulated eleven populations with identical treatment effect distributions based on patient factors. The populations varied in the extent that treatment effect heterogeneity influenced treatment choice. We used the generalized random forest application (CFA-GRF) to estimate patient-specific treatment effects for each population. Average differences between true and estimated effects for patient subsets were evaluated. RESULTS: CFA-GRF performed well across the population when treatment effect heterogeneity did not influence treatment choice. Under essential heterogeneity, however, CFA-GRF yielded treatment effect estimates that reflected true treatment effects only for treated patients and were on average greater than true treatment effects for untreated patients. CONCLUSIONS: Patient-specific estimates produced by CFAs are sensitive to why patients in real-world practice make different treatment choices. Researchers using CFAs should develop conceptual frameworks of treatment choice prior to estimation to guide estimate interpretation ex post.

Construct validity of the 12-item Short Form Health Survey (SF-12) version 2 and the impact of lifestyle modifications on the health-related quality of life among Indian adults with prediabetes: results from the D-CLIP trial.

PURPOSE: This study aimed to validate the factor structure of the 12-item Short-Form (SF-12) health-related quality of life (HRQOL) survey for Indian adults and assess the impact of lifestyle modification on the SF-12 of Indian adults with prediabetes. METHODS: To validate the context-specific construct of the SF-12, two-factor confirmatory factor analysis (CFA) was performed using data from 1285 adults residing in Chennai, India, who screened for the Diabetes Community Lifestyle Improvement Program (D-CLIP). D-CLIP was a randomized controlled trial of 578 participants with prediabetes (283 treatment, 293 control), focusing on the effect of lifestyle modifications on the prevention of diabetes. Physical and mental component scores (PCS and MCS) were computed by using CFA standardized factor loadings. Multiple linear regression was subsequently conducted to estimate the effect of lifestyle modification on post-study changes of PCS and MCS among D-CLIP participants. RESULTS: Cronbach's alpha and CFA fit indices demonstrated acceptable reliability and model fit of the SF-12 for Indian adults. The intervention group showed greater mean change in PCS after study participation compared to the controls (1.63 ± 0.82, p = 0.046); no significant difference was observed for MCS between two groups (1.00 ± 0.85, p = 0.242). CONCLUSION: The study confirmed that the SF-12 is suitable for assessing the physical and mental health dimensions of HRQOL for Indian adults. Our findings suggest that the benefits of diabetes prevention lifestyle modification strategies may primarily enhance the physical well-being of adults with prediabetes. Further studies validating the SF-12 in a broader Asian Indian population are needed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01283308.

Factor structure of psychosis screening questionnaire in Ugandan adults.

BACKGROUND: Psychotic disorders are common and contribute significantly to morbidity and mortality of people with psychiatric diseases. Therefore, early screening and detection may facilitate early intervention and reduce adverse outcomes. Screening tools that lay persons can administer are particularly beneficial in low resource settings. However, there is limited research evaluating the validity of psychosis screening instruments in Uganda. We aimed to assess the construct validity and psychometric properties of the Psychosis Screening Questionnaire (PSQ) in Uganda in a population with no history of a psychotic disorder. METHODS: The sample consisted of 2101 Ugandan adults participating as controls in a larger multi-country case-control study on psychiatric genetics who were recruited between February 2018 and March 2020. Participants were individuals seeking outpatient general medical care, caretakers of individuals seeking care, and staff or students recruited from five medical facilities that were age 18 years or older and able to provide consent. Individuals were excluded who had acute levels of alcohol or substance use, including being under inpatient hospitalization or acute medical care for one of these conditions. We used confirmatory factor analysis (CFA) and item response theory (IRT) to evaluate the factor structure and item properties of the PSQ. RESULTS: The overall prevalence screening positive for psychotic symptoms was 13.9% 95% CI (12.4,15.4). "Strange experiences" were the most endorsed symptoms 6.6% 95% CI (5.6,7.8). A unidimensional model seemed to be a good model or well-fitting based on fit indices including the root mean square error of approximation (RMSEA of 0.00), comparative fit index (CFI of 1.000), and Tucker-Lewis Index (TLI of 1.000). The most discriminating items along the latent construct of psychosis were items assessing thought disturbance followed by items assessing paranoia, with a parameter (discrimination) value of 2.53 and 2.40, respectively. CONCLUSION: The PSQ works well in Uganda as an initial screening tool for moderate to high-level of psychotic symptoms.

Development and validation of a scale to measure hypertensive Chinese individual's behavior toward salt reduction consumption.

OBJECTIVE: This study aimed to develop and validate the Salt Reduction Behavior Scale (SRBS) to measure the behavior of hypertensive Chinese individuals in adhering to salt reduction practices. METHODS: The SRBS was constructed based on the Health Belief Model, consisting of five constructs: knowledge, perceived severity, perceived benefits, perceived barriers, and cues to action. Data were collected from 2,082 hypertensive patients in Beijing, China, who completed a questionnaire administered through an online platform. Kaiser-Meyer-Olkin (KMO) test was used to assess the adequacy of the sample and the Bartlett's test of sphericity to examine the factorability of the dataset. Confirmatory Factor Analysis (CFA) was used to assess the structural validity and reliability of the SRBS. RESULTS: The KMO analysis yielded a notably elevated value of 0.95, indicating that the data was highly suitable for Exploratory Factor Analysis (EFA). Bartlett's test of sphericity yielded a statistically significant test statistic (P < 0.001). The 32-item SRB questionnaire demonstrated strong internal consistency with a Cronbach's alpha coefficient of 0.923. A second-order Confirmatory Factor Analysis (CFA) revealed that, after removing the unrelated construct of barriers, SRB could be represented by four sub-constructs: knowledge, severity, benefits, and action. The final version of the SRBS consists of 21 items. These items displayed high factor loadings, indicating a strong relationship between the items and their respective sub-constructs. The discriminant validity analysis revealed that the SRBS sub-constructs were distinct from each other. The SRBS scores were positively correlated with self-reported salt reduction practices. This demonstrates that individuals with higher SRBS scores were more likely to engage in actual salt reduction behaviors, indicating concurrent validity. CONCLUSION: The results illustrate that the Salt Reduction Behavior Scale is a robust and comprehensive instrument for assessing salt reduction behavior among hypertensive Chinese individuals. The scale's specific sub-constructs provide a detailed understanding of their knowledge, attitudes, and practices related to salt consumption. Healthcare professionals and policymakers can utilize this tool to tailor interventions and educational programs to encourage healthier dietary habits, thereby reducing the risk of cardiovascular diseases in China.

Measuring depressive symptoms among Latinos in the US: a psychometric evaluation of the CES-D Boston form.

PURPOSE: We present a psychometric evaluation of the Center for Epidemiologic Studies Depression Boston Form (CES-D-B) for use with different Latino subgroups as there is inconsistency regarding its performance across subgroups of Latinos, a large and rapidly growing cultural group in the United States. METHODS: We evaluated the reliability and structural validity of the scores generated by the CES-D-B using four distinct Latino samples residing in US: Mexicans, Venezuelans, Cubans, and "other Latinos" (total N = 1033). To further explore structural validity of CES-D-B scores, we conducted measurement invariance analyses across different countries of origin, gender groups, educational levels, and languages of assessment (English, Spanish). RESULTS: For all four samples, CES-D-B scores were highly reliable as indicated with the coefficients ranging from 0.82 to 0.88, and the factor structure provided an adequate fit to the data with the fit indices CFI/TLI ranging from 0.96 to 0.99, RMSEA estimates between 0.02 and 0.07, and SRMR estimates between 0.02 and 0.04. While measurement invariance analyses for different educational levels indicated scalar invariance across all samples, the same level of measurement equivalency was achieved only for Mexicans and Venezuelans with varying gender and languages of assessment. CONCLUSIONS: The findings indicated that CES-D-B scores are internally consistent, possess a strong four-factor structure, and have somewhat equivalent psychometric properties across diverse Latino groups. Findings from this study highlight the importance of considering gender and languages of assessment when assessing depressive symptoms of various Latino subgroups.

Analysis of interventional treatment options of the common femoral artery - a retrospective single center experience.

Background: Due to the rapid development of treatment techniques of peripheral arterial disease (PAD) treatment is nowadays predominantly interventional. An exception are lesions of the common femoral artery (CFA), which should be treated surgically according to vascular guidelines. However, recent evidence has shown that endovascular techniques, e.g. stenting, have comparable clinical outcomes while causing fewer complications. The aim of the present analysis was to evaluate the therapeutic success of endovascular therapy of CFA lesions in a single center, all - comers registry. Patients and methods: All patients who were treated for a CFA lesion at the Department of Internal Medicine I of the University Hospital Jena in the period from 01/2017 to 12/2020 were included. Treatment success was determined by evaluating the ankle-brachial-index (ABI) pre- and post-interventional as well as after follow-up (FU), measuring walking distance (WD) and by target revascularization rate (TLR) and primary patency rate (PPR). Results: The analysis included 109 patients with a mean age of 73.4 years, with 67% (73) of those being men. 72 patients received interventional treatment, whereas 33 were treated surgically and 4 conservatively. Resting ABI in the overall cohort showed an increase from 0.5 to 0.7 post intervention (p=<0.05; mean FU-time: 6.5 months). In the interventional cohort ABI increases from 0.6 to 0.8 (p=<0.05; mean FU-time: 5,8 months) at FU and from 0.3 to 0.6 (p=<0.05; mean FU-time: 8,8 month) in the surgically treated group. The WD improved in the whole collective from 116.5 meter (m) to 152.5 m (p=<0.05). The TLR showed no significant difference with 8.1% after interventional treatment and 6.1% after vascular surgery in the present analysis (p=0.72) as well as PPR with 89.8% after EVT and 90.9% after surgical approach (p=0.87). The intra-/postinterventional complication rate was 5.5% in the intervention group, compared to postoperative complication rate of 15.2% in the surgically treated group. Conclusions: The present analysis demonstrates that even in a real-world, all-comers collective, interventional therapy for CFA lesions was safe and equally effective as the surgically treated patient cohort. Continuing to generate registry data is important to eventually initiate a paradigm shift.

A study of acoustic-light-thermal effects on pedestrians' overall comfort in a Cfa-climate campus during the summer.

The environmental quality, in terms of acoustic, visual, and thermal environments, significantly affects people's comfort levels. Along these lines, in this work, their comprehensive impact on people's overall comfort was systematically explored. Pedestrians' outdoor neutral points on various environmental parameters were found by performing linear regressions. Similarly, people's thermal perceptions (indicated by neutral temperatures, NT) were found to vary for both acoustic and light environments. They would be increasingly heat sensitive (R2 increases) in a noisier environment while the NTs varied for either sound or light intensity levels. From our analysis, it was demonstrated that people's overall comforts were negatively correlated with these parameters in different degrees. This work provides valuable insights for future urban design and planning studies to create better outdoor environments.

Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats.

This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17ß-estradiol (28 µg/kg/day) or placebo for 21 days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.

Cultural landscapes in climate change: A framework for resilience in developing countries.

Cultural landscapes, particularly cities with rich historical and cultural heritage, play a crucial role in bolstering the resilience of local communities. The occurrence of climate change-induced phenomena jeopardizes cultural landscapes, resulting in the deterioration of historical structures, natural landscapes, cultural heritage, the economy, and the livelihoods of residents in these areas. Therefore, adopting a resilient approach is essential for the integrated management of cultural landscapes. This study develops a model for enhancing cultural landscape resilience to climate change in Nishapur, a historical and cultural city in Iran. Through desk studies, factors affecting the resilience of cultural landscapes to climate change were extracted in the context of developing countries. Subsequently, a model was developed based on the frequency of the occurrence of dimensions and indicators. Snowball sampling was used to distribute questionnaires to 310 members of the academic and professional communities in the field. Next, confirmatory factor analysis (CFA) was conducted using IBM SEM-AMOS to analyze the data and measure the reliability and validity of the model. The findings indicate that the driving factors of change, such as changes in livelihood and social issues, historical fabric and physical environment, natural hazards, biodiversity patterns, and management patterns, can significantly affect the resilience of cultural landscapes to climate change. The developed model can contribute to policymaking in various fields, including urban design and planning, economics, sociology, and cultural heritage conservation. This can play a vital role in creating cultural landscapes that are resilient to the increasing impacts of climate change.

Evaluating the docetaxel effect in an animal model of polyarthritis.

Rheumatoid arthritis (RA) is immune-mediated, inflammatory disease that affects synovial joints, and characterized by inflammatory changes in synovial tissue, cartilage, bone, and less commonly in extra-articular structures. Docetaxel (DTX) is a semi-synthetic anti-neoplastic medication. Peptidyl-arginine deiminase type 4 (PAD4) is expressed in macrophages and neutrophils in RA synovial membrane. Their effectiveness is in producing anti-cyclic citrullinated peptide antibodies (ACPA)-targeted citrullinated neoepitopes. AIM: To evaluate the anti-inflammatory effects of DTX in RA and the effect of methotrexate on PAD4 to investigate its potential as an RA biomarker. METHODS: Forty male Wistar rats were divided into five groups of eight rats. Healthy rats formed the control group. The Second Group to Fifth group were induced with Complete Freund's adjuvant. The third group received DTX at a dosage of 1 mg/kg on alternate days, as determined by a preliminary experiment. The fourth group was given 1 mg/kg/week of methotrexate intraperitoneally. The fifth group was treated with a half dose of DTX and methotrexate simultaneously. RESULTS: Significant Arthritis index and knee joint circumference decrease in the DTX group. No significant difference in body weight, platelet-lymphocyte ratio, and white blood cell count between the groups. Neutrophile lymphocyte ratio showed weak correlation with ACPA, while PAD4 showed good correlation with RA markers. Level of ACPA, PAD4, TNF-α, IL-1ß, and VEGF significantly decreased in the DTX group than induction group (p < 0.05). CONCLUSION: DTX reduces the progression and joint destruction in rats induced by Complete Freund's Adjuvant which may due to inhibition of PAD4, TNF-α, IL-1ß, VEGF, and ACPA. Also, methotrexate exhibited anti PAD4 effect.

Onosma bracteatum Wall Aqueous-Ethanolic Extract Suppresses Complete Freund's Adjuvant-Induced Arthritis in Rats via Regulation of TNF-α, IL-6, and C-Reactive Protein.

Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous-ethanolic extract of O. bracteatum leaves (AeOB) in a rat model of complete Freund's adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC50 of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves.

Arbutin attenuates CFA-induced arthritis by modulating expression levels of 5-LOX, NF­κB, IL-17, PGE-2 and TNF-α.

Arbutin, a naturally soluble glycosylated phenol has antioxidant, antimicrobial, antitumor and anti-inflammatory properties. The current exploration appraises the treatment of arthritis by use of Arbutin (25, 50 and 100 mg/kg) orally in CFA-induced rat arthritis model. Body weight changes, paw size, and joint diameter were recorded till the 28th day in the arthritic-induced rats. Hematological, biochemical, oxidative and inflammatory biomarkers were measured through the blood samples of anesthetized rats. Arbutin markedly decreased paw volume, PGE-2, anti-CCP and 5-LOX levels, however, maintained metabolic and hematological balance and prevented weight loss. Radiology and histology changes improved significantly in the ankle joints of rats. Moreover, Arbutin increased gene pointers such as IL-10 and IL-4 while significantly reducing the levels of CRP and WBCs, whereas Hb, platelets and RBCs count markedly raised in post-treatments. Antioxidant levels of SOD, CAT and GSH were improved and MDA level was reduced in treated groups. Rt-PCR investigation showed a significant reduction of the interleukin-1ß, TNF-α, interleukin-6, cyclooxygenase-2, NF-κB and IL-17 and increased expression of gene pointers like IL-4, and IL-10 in treated groups. Assessment of molecular docking revealed a strong binding interaction of Arbutin against 5-LOX, IL-17, TNF-alpha and interleukin-6, cyclooxygenase-2, nuclear factor-κB, IL-4 and iNOS providing a strong association between experimental and theoretical results. As a result, Arbutin has significantly reduced CFA-induced arthritis by modulation of anti-inflammatory cytokines, i.e., IL-10 and IL-4, the pro-inflammatory cytokines panel such as NF-κB, TNF-alpha, IL-1ß, IL-6, PGE-2, 5-LOX and COX-2 and oxidative biomarkers.

Galantamine mitigates testicular injury and disturbed spermatogenesis in adjuvant arthritic rats via modulating apoptosis, inflammatory signals, and IL-6/JAK/STAT3/SOCS3 signaling.

Rheumatoid arthritis (RA) affects the joints and the endocrine system via persistent immune system activation. RA patients have a higher frequency of testicular dysfunction, impotence, and decreased libido. This investigation aimed to evaluate the efficacy of galantamine (GAL) on testicular injury secondary to RA. Rats were allocated into four groups: control, GAL (2 mg/kg/day, p.o), CFA (0.3 mg/kg, s.c), and CFA + GAL. Testicular injury indicators, such as testosterone level, sperm count, and gonadosomatic index, were evaluated. Inflammatory indicators, such as interleukin-6 (IL-6), p-Nuclear factor kappa B (NF-κB p65), and anti-inflammatory cytokine interleukin-10 (IL-10), were assessed. Cleaved caspase-3 expression was immunohistochemically investigated. Protein expressions of Janus kinase (JAK), signal transducers and activators of transcription (STAT3), and Suppressors of Cytokine Signaling 3 (SOCS3) were examined by Western blot analysis. Results show that serum testosterone, sperm count, and gonadosomatic index were increased significantly by GAL. Additionally, GAL significantly diminished testicular IL-6 while improved IL-10 expression relative to CFA group. Furthermore, GAL attenuated testicular histopathological abnormalities by CFA and downregulated cleaved caspase-3 and NF-κB p65 expressions. It also downregulated JAK/STAT3 cascade with SOCS3 upregulation. In conclusion, GAL has potential protective effects on testicular damage secondary to RA via counteracting testicular inflammation, apoptosis, and inhibiting IL-6/JAK/STAT3/SOCS3 signaling.

In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis.

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28 days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40 mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

Synthesized pyrrole ester ameliorates adjuvant­induced arthritis in Wistar rats by alleviating inflammation and downregulating the pro­inflammatory cytokines.

Piperine is an amide alkaloid responsible for producing the pungent smell that comes from black pepper. Piperine has been explained to exhibit significant properties such as anti-rheumatic, anti-inflammatory, and antihypertensive effects. The aim of the study was to synthesize pyrrole ester from piperine and evaluate its anti-arthritis effects in adjuvant-induced arthritis female Wistar rats. In this study, pyrrole ester (AU-5) was designed, synthesized and evaluated for ant-arthritic activity in adjuvant-induced arthritis Wistar rats. The synthesized pyrrole ester (AU-5) was administered in three selected doses (20, 10 and 5 mg/kg) to the arthritic-induced model. The administered ester significantly inhibited the increase in arthritis index, paw and ankle joint swelling compared to the arthritic control group. Similarly, the treated rats exhibited a remarkable increase in body weight increase, improved haematological, biochemical, histopathological and radiological parameters. Moreover, the excess production of rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was noticeably attenuated in all AU-5-treated rats. However, the spleen index, tumour necrosis factor (TNF-α) and interleukin-6 (IL-6) were distinctly lowered compared to arthritic control rats. Moreover, AU-5 showed promising liver protection by lowering the level of liver function markers Serum glutamic pyruvic transaminase (SGPT), Serum glutamic-oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) in serum. Henceforth, it might be concluded that AU-5 has an anti-arthritic effect which can be credited to the down regulation of inflammatory markers and the pro-inflammatory cytokines.

Anti-arthritic and immunomodulatory efficacy of Micromeria biflora Benth extract and its fractions in rats by restoring oxidative stress, metalloproteinases, pro-inflammatory and anti-inflammatory cytokines network.

Micromeria biflora (M.B) Benth has proven anti-inflammatory efficacy, thereby, the goal of the current investigation was to assess the anti-arthritic potential of M.B ethanolic extract and fractions as well as to investigate the likely mechanism of action. The effectiveness of M.B against acute arthritic manifestations was assessed using an arthritic model prompted by formaldehyde, whereas a chronic model was developed using an adjuvant called Complete Freund's in Sprague-Dawley rats. Weekly evaluations were conducted for parameters involving paw volume, body weight, and arthritic score; at the completion of the CFA model, hematological, biochemical and oxidative stress parameters as well as the level of various mediators (PGE2, IL-1ß, TNFα, IL6, MMP2, 3, 9, VEGF, NF-ĸB, IL-10, and IL-4) were evaluated. The results demonstrated the plant's ability to treat arthritis by showing a significant decrease in paw volume, arthritic score, and histological characteristics. The levels of NF-ĸB, MMP2, 3, 9, IL6, IL1ß, TNFα, and VEGF were all significantly reduced after treatment with plant extract and fractions. Plant extract and its fractions substantially preserved body weight loss, oxidative stress markers and levels of IL-4 and 1L-10. PGE2 levels were also shown to be reduced in the treatment groups, supporting the M.B immunomodulatory ability. Hematological and biochemical indicators were also normalized after M.B administration. Outcomes of the study validated the anti-arthritic and immunomodulatory attributes of M.B probably through modulating oxidative stress, inflammatory, pro-inflammatory and anti-inflammatory biomarkers.

Psychometric properties of the Interpersonal Emotion Regulation Questionnaire in a community sample of the Portuguese population.

BACKGROUND: Intrapersonal aspects of emotion regulation have been at the forefront of research, while interpersonal aspects have received less attention. The Interpersonal Emotion Regulation Questionnaire (IERQ) was developed to address this issue. However, this scale was neither adapted nor validated for European Portuguese. AIMS: The present study aims to adapt the IERQ to European Portuguese and explore the preliminary psychometric properties of the IERQ in a community sample, through confirmatory factor analysis (CFA). Construct validity was further supported by examining convergent validity with ERQ subscales. METHOD: Using a cross-sectional design, individuals were recruited online. Self-report questionnaires were used, namely the IERQ and the Emotion Regulation Questionnaire (ERQ). RESULTS: The four-factor structure was confirmed through CFA. IERQ subscales correlated positively with the dimensions of the ERQ of cognitive reappraisal and correlated negatively with experiential suppression. CONCLUSIONS: This preliminary study showed that the IERQ has adequate psychometric properties in a Portuguese sample and supports that this instrument can be used to assess interpersonal emotion regulation strategies in non-clinical samples.