Effect of Boswellia on Adjuvant Induced Rheumatoid Arthritis in Experimental Animals

Arthritis is the most common systemic connective tissue disease. About 1% of the world's population is affected by RA; women are three times more often than men. Onset is most frequent between the ages of 40 and 50 years, but people of any age can be affected. Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible joints. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays an important role in both its chronicity and progression.The new trend of medical treatment of rheumatoid arthritis seeks new drugs with more efficacy and fewer side effects. Since tumor necrosis factor alpha (TNF-α) as well as other cytokines act as key players in the development of arthritis.Studies in the United States and Europe have shown that their use is less common in clinical settings, but has become increasingly more in recent years as scientific evidence about the effectiveness of herbal medicine has become more widely available.  The present work investigates the effect of Boswellia on Adjuvant induced RA in Experimental Animals

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Metabolomic profiling and biological evaluations of <i>Spongia irregularis</i>-associated actinomycetes supported by multivariate statistical analysis

AimMetabolomic analysis using LC–HRESIMS of 12 extracts of Spongia irregularis-associated actinomycetes for dereplication purposes in addition to evaluation of cytotoxic and antiviral activities of the extracts.Methods and resultsIn this study, three actinomycetes belonging to the genera Micromonospora, Streptomyces, and Rhodococcus were recovered from the marine sponge Spongia irregularis. Applying the OSMAC approach, each strain was fermented on four different media, resulting in 12 extracts. All extracts were subjected to metabolomic analysis using LC–HRESIMS for dereplication purposes. Multivariate data statistical analysis was carried out for the differentiation between extracts. Additionally, the cytotoxic and anti-hepatitis C virus (anti-HCV) potentials of extracts were evaluated. Most of extracts showed strong to moderate cytotoxicity effects against HepG-2, CACO-2, and MCF-7 cell lines with a general IC50 range of 2.8–8.9 µg/ml. Moreover, the extracts of Micromonospora sp. UR44 using ISP2 and OLIGO media and Streptomyces sp. UR32 using ISP2 medium exhibited anti-HCV activity with IC50 of 4.5 ± 0.22, 3.8 ± 0.18, and 5.7 ± 0.15 µM, respectively.ConclusionMetabolomic analysis of 12 extracts of S. irregularis-associated actinomycetes led to the identification of a large number of secondary metabolites. Morever, investigation of cytotoxic and antiviral activities of the extracts revealed that only three extracts exhibited antiviral activity and seven extracts exhibited cytotoxic activity

Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies

Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography–mass spectrometry (GC–MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC$_{50}$ of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2–p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

AbstractA new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e, 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR