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Introduction: Growing antimicrobial resistance (AMR) and decreasing efficacy of the available antimicrobials have become a significant public health concern. The antimicrobial stewardship program (ASP) ensures the appropriate use of antimicrobials and mitigates resistance prevalence through various interventions. One of the core components of the ASP is to educate healthcare workers (HWs). Therefore, this study aims to identify the impact of a pharmacist-led educational intervention targeting knowledge, attitude, and practices regarding rational antibiotic use among healthcare professionals in a secondary care hospital in Punjab. Methods: This is a single-center, questionnaire-based, pre-post interventional study conducted over a six-month time period. Data analysis was conducted using SPSS version 26. Results: Regarding the pre-interventional knowledge, attitude, and practice (KAP) score of the respondents, 90.3% had a good knowledge score, 81.5% had a positive attitude, and 72.3% of HWs (excluding doctors) had a good practice score. Additionally, 74.6% of the doctors had a good practice score. After educational intervention, there was a significant improvement in the knowledge, attitude, and practice of the respondent HWs (p-value <0.001). Furthermore, males have higher knowledge scores compared to females in the pre- and post-intervention stages (p-value <0.05), and doctors differ from nurses regarding knowledge scores in both pre- and post-intervention stages. Conclusion: Considering educational programs as the backbone of the ASP, it is imperative to sustain efforts in the ongoing educational programs of HWs to foster high awareness and adherence to the ASP among HWs. [ABSTRACT FROM AUTHOR]

Triggering through abiotic stress, including chemical triggers like heavy metals, is a new technique for drug discovery. In this research, the effect of heavy metal Nickel on actinobacteria Streptomyces sp. SH-1327 to obtain a stress-derived compound was firstly investigated. A new compound cyclo-(D)-Pro-(D)-Phe (CDPDP) was triggered from the actinobacteria strain SH-1327 with the addition of nickel ions 1 mM. The stress compound was further evaluated for its antioxidant, analgesic, and anti-inflammatory activity against rheumatoid arthritis through in-vitro and in-vivo assays in albino mice. A remarkable in-vitro antioxidant potential of CDPDP was recorded with the IC50 value of 30.06 ± 5.11 μg/ml in DPPH, IC50 of 18.98 ± 2.91 against NO free radicals, the IC50 value of 27.15 ± 3.12 against scavenging ability and IC50 value of 28.40 ± 3.14 μg/ml for iron chelation capacity. Downregulation of pro-inflammatory mediators (NO and MDA), suppressed levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-Iβ) and upregulation of expressions of anti-oxidant enzymes (GSH, catalase, and GST) unveiled its anti-inflammatory potential. CDPDP was analyzed in human chondrocyte cell line CHON-001 and the results demonstrated that CDPDP significantly increased cell survival, and inhibited apoptosis of IL-1β treated chondrocytes and IL-1β induced matrix degrading markers. In addition, to evaluate the mitochondrial fitness of CHON-001 cells, CDPDP significantly upregulated pgc1-α, the master regulator of mitochondrial biogenesis, indicating that CDPDP provides protective effects in CHON-001 cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of the CDPDP showed that CDPDP is safe in cases of hepatotoxicity, cardiotoxicity, and cytochrome inhibition. Furthermore, docking results showed good binding of CDPDP with IL-6-17.4 kcal/mol, and the simulation studies proved the stability between ligand and protein. Therefore, the findings of the current study prospect CDPDP as a potent anti-oxidant and a plausible anti-arthritic agent with a strong pharmacokinetic and pharmacological profile. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis and osteoarthritis overlap many molecular mechanisms of cartilage destruction. Wear and tear in cartilage is chondrocyte-mediated, where chondrocytes act both as effector and target cells. In current study, role ofβ2-AR was studied in chondrocytes both in vitro and in vivo. High grade inflammation in vitro and in vivo diseasemodels led to decline in anti-inflammatoryβ2-AR signaling and use of ß2-AR agonist attenuated arthritis symptoms. Detailed analysis in chondrocytes revealed that Isoprenaline (ISO) and Salbutamol (SBT) increased cell viability and relative Bcl-2 expression, meanwhile, decreased proteins levels of TNF-a, IL-6andIL-8 in arthritic chondrocytes when compared with control, respectively. SBT preserved physiological concentration of antioxidant enzymes (CAT, POD, SOD and GSH) in cartilage homogenates and ISO inhibited IL-1ß-mediated genotoxicity in arthritic chondrocytes. Moreover, β2-AR agonist increased mitochondrial biogenesis and proteoglycan biosynthesis by upregulating the gene expression of PGC1-a, NRF2 and COL2A1, Acan, respectively. ISO and SBT inhibited extracellular matrix (ECM) degradation by downregulating the gene expression of MMP1, MMP3, MMP9 and ADAMTS5 in vitro and in vivo study. In mechanism, β2-AR agonists decreasedβ-arrestin and GRK2 pathway, and as a resultmice receiving SBT did not exhibit severe disease. Hence our data suggestβ2-AR agonist administered at disease onset can inhibit receptor internalization by downregulating the expression ofβ-arrestin and GRK2 in chondrocytes. [ABSTRACT FROM AUTHOR]