Lawsonia inermis seeds cotyledon and coat extracts as a potential antimicrobial agent

Background: The plant Lawsonia inermis, which is a member of the Lythraceae family, has long been used to cure a number of diseases. Previous studies have demonstrated the antibacterial capabilities of the plant's components. However, neither the efficiency of these extracts on bacterial strains that are antibiotic-resistant nor a systematic analysis of the extracts from the various seed components have been conducted. Methods: The coat part was separated from the cotyledon. Each part was pulverized and extracted with ethanol, acetone, and hexane. The inhibitory effects of the resulting extracts were tested on three pathogenic bacterial strains and a fungus. The effect of the extracts on antibiotic-resistant bacteria was also evaluated.Results: When tested against pathogenic bacteria (Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumonia, and Candida albicans), L. inermis seed parts (cotyledon and coat) showed varying levels of antibacterial and antifungal activity. In which the ethanolic extract outperformed the acetonic extract in effectiveness. The minimal inhibitory concentration (MIC) for each pathogenic microorganism was established. Utilizing the extract yield, total antibacterial activity (TAA) was calculated. Lawsonia inermis seed components inhibited antibiotic-resistant strains of S. aureus and P. aeruginosa, with strong antibacterial activity seen in aqueous extracts of their cotyledons and coats.Conclusion: We summarize that Lawsonia inermis seed extracts, which have historically been used as secure antimicrobials for human healthcare and cosmetics have the potential to replace current antimicrobial agents that are no longer effective. Moreover, may be a promising source for the isolation of potent drugs for the treatment of bacterial diseases.Keywords: Lawsonia inermis; Henna; Extract; Seeds; Bacterial Infection; Antibiotics Resistance   

Notch Signaling Inhibition by LY411575 Attenuates Osteoblast Differentiation and Decreased Ectopic Bone Formation Capacity of Human Skeletal (Mesenchymal) Stem Cells

Background. Chemical biology approaches using small molecule inhibitors targeting specific signaling pathways are useful tools to dissect the molecular mechanisms governing stem cell differentiation and for their possible use in therapeutic interventions. Methods. Stem cell signaling small molecule library functional screen was performed employing human bone marrow skeletal (mesenchymal) stem cells (hBMSCs). Alkaline phosphatase (ALP) activity and formation of mineralized matrix visualized by Alizarin red staining were employed as markers for osteoblastic differentiation. Global gene expression profiling was conducted using the Agilent microarray platform, and data normalization and bioinformatics were performed using GeneSpring software. Pathway analyses were conducted using the Ingenuity Pathway Analysis (IPA) tool. In vivo ectopic bone formation was performed using hBMSC mixed with hydroxyapatite–tricalcium phosphate granules that were implanted subcutaneously in 8-week-old female nude mice. Hematoxylin and eosin staining and Sirius red staining were performed to identify bone formation in vivo. Results. Among the tested molecules, LY411575, a potent γ-secretase and Notch signaling inhibitor, exhibited significant inhibitory effects on osteoblastic differentiation of hBMSCs manifested by reduced ALP activity, mineralized matrix formation, and decreased osteoblast-specific gene expression as well as in vivo ectopic bone formation. Global gene expression profiling of LY411575-treated cells revealed changes in multiple signaling pathways, including focal adhesion, insulin, TGFβ, IL6, and Notch signaling, and decreased the expression of genes associated with functional categories of tissue development. Among the affected signaling networks were TGFβ1, SPP1, and ERK regulatory networks. Conclusions. We identified γ-secretase inhibitor (LY411575) as a potent regulator of osteoblastic differentiation of hBMSC that may be useful as a therapeutic option for treating conditions associated with ectopic bone formation

Stem cell library screen identified ruxolitinib as regulator of osteoblastic differentiation of human skeletal stem cells

Abstract Background Better understanding of the signaling pathways that regulate human bone marrow stromal stem cell (hBMSC) differentiation into bone-forming osteoblasts is crucial for their clinical use in regenerative medicine. Chemical biology approaches using small molecules targeting specific signaling pathways are increasingly employed to manipulate stem cell differentiation fate. Methods We employed alkaline phosphatase activity and staining assays to assess osteoblast differentiation and Alizarin R staining to assess mineralized matrix formation of cultured hBMSCs. Changes in gene expression were assessed using an Agilent microarray platform, and data normalization and bioinformatics were performed using GeneSpring software. For in vivo ectopic bone formation experiments, hMSCs were mixed with hydroxyapatite–tricalcium phosphate granules and implanted subcutaneously into the dorsal surface of 8-week-old female nude mice. Hematoxylin and eosin staining and Sirius Red staining were used to detect bone formation in vivo. Results We identified several compounds which inhibited osteoblastic differentiation of hMSCs. In particular, we identified ruxolitinib (INCB018424) (3 μM), an inhibitor of JAK-STAT signaling that inhibited osteoblastic differentiation and matrix mineralization of hMSCs in vitro and reduced ectopic bone formation in vivo. Global gene expression profiling of ruxolitinib-treated cells identified 847 upregulated and 822 downregulated mRNA transcripts, compared to vehicle-treated control cells. Bioinformatic analysis revealed differential regulation of multiple genetic pathways, including TGFβ and insulin signaling, endochondral ossification, and focal adhesion. Conclusions We identified ruxolitinib as an important regulator of osteoblast differentiation of hMSCs. It is plausible that inhibition of osteoblast differentiation by ruxolitinib may represent a novel therapeutic strategy for the treatment of pathological conditions caused by accelerated osteoblast differentiation and mineralization

Knowledge, perceptions, and readiness of telepharmacy among community pharmacists

Telepharmacy is a practical part of telemedicine that refers to providing pharmaceutical services within the scope of the pharmacist's obligations while maintaining a temporal and spatial distance between patients, users of health services, and healthcare professionals. The present study was a cross-sectional study conducted among community pharmacists in Saudi Arabia between March and May 2022 to assess their knowledge, perceptions, and readiness for telepharmacy. The survey was filled out by 404 respondents. The majority of respondents were male (59.90%) and the age of more than half of them was between 30 and 39 years old (54.46%). Most participants worked in urban areas (83.66%), and 42.57% had less than five years of experience in a pharmacy. Most participants agreed that telepharmacy is available in Saudi Arabia (82.67%). Approximately 70% of pharmacists felt that telepharmacy promotes patient medication adherence, and 77.72% agreed that telepharmacy increases patient access to pharmaceuticals in rural areas. More than 72% of pharmacists said they would work on telepharmacy initiatives in rural areas for free, and 74.26% said they would work outside of usual working hours if necessary. In the future, this research could aid in adopting full-fledged telepharmacy pharmaceutical care services in Saudi Arabia. It could also help academic initiatives by allowing telepharmacy practice models to be included as a topic course in the curriculum to prepare future pharmacists to deliver telepharmacy services

The influence of telemedicine in primary healthcare on diabetes mellitus control and treatment adherence in Riyadh region

Several studies have found that telemedicine has the potential to enhance the outcomes of patients with diabetes. This study aimed to determine the impact of telemedicine on the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) in Saudi Arabia. We conducted a cross-sectional study among T2DM patients in selected primary healthcare centers in Riyadh, Saudi Arabia, from March 1, 2023, to August 20, 2023. We looked at how telemedicine affected HbA1c control, adherence, the number of diabetic complications, and polypharmacy using adjusted multivariable logistic regression models. Among the 583 patients, 140 (24.05 %) received care via telemedicine, while 442 (75.95 %) received in-person care. Patients who utilized telemedicine had significantly better glycemic control than those who received in-person care only (AOR = 5.123, 95 % CI = 3.107–8.447). Telemedicine also showed positive effects on treatment adherence (AOR = 2.552, 95 % CI = 1.6284–4.2414). Telemedicine can effectively reduce diabetic complications (AOR = 0.277, 95 % CI = 0.134–0.571). Regarding polypharmacy, patients with telemedicine use were less likely to report polypharmacy (AOR = 0.559, 95 % CI = 0.361–0.866). Telemedicine is considered one of the factors that improve HbA1c management and might increase therapeutic adherence and reduce diabetic complications and polypharmacy

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research