Corrigendum to "A narrative review of approved and emerging anti-obesity medications" [Saudi Pharm. J. 31(10) (2023) 101757].

[This corrects the article DOI: 10.1016/j.jsps.2023.101757.].

A narrative review of approved and emerging anti-obesity medications.

Background: Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping. Objective: This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety. Methods and materials: We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies. Results: Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity. Conclusion: The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.

High throughput biochemical profiling, and functional potential analysis for valorization of grape peduncles.

Vitis vinifera L., commonly known as grape is a major fruit crop in the world. Grapes seem to confer health benefits due to their chemical components, biological and antioxidant activities. The present study is conducted to evaluate the biochemical constituents, antioxidant, and antimicrobial potential of ethanolic grape peduncles (EGP) extract. The result of phytochemical analysis revealed the presence of various phytochemicals such as flavonoid, tannin, carbohydrates, alkaloids, cardiac glycoside, phenol, steroid, terpenoids, quinones and anthraquinones. Furthermore, total phenolic content (TPC) and total flavonoid contents (TFC) were 7.35 ± 0.25 mg GAE/g (Gallic Acid Equivalent per gram) and 29.67 ± 0.13 mg QE/g (Quercetin Equivalent per gram) respectively. DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging assay revealed IC50 = 159.3 µg/mL. The antibacterial and antifungal study disclosed that the extract was highly potent against Salmonella typhi with maximum zone of inhibition of 27.2 ± 1.60 mm and Epidermophyton floccosum with 74 ± 1.81% inhibition. The extract was analyzed for its cytotoxicity and antileishmanial activity and showed no activity against HeLa cell line and promastigotes of Leishmania major. Elements Fe, Mn, Ni, Pb and Cd were determined by atomic absorption spectroscopy and approximately 50 compounds were identified by Gas Chromatography-Mass Spectrometry (GC-MS). Current work suggest that grape peduncles can be a promising source of bioactive medicinal component.

Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.

Identification of NS2B-NS3 Protease Inhibitors for Therapeutic Application in ZIKV Infection: A Pharmacophore-Based High-Throughput Virtual Screening and MD Simulations Approaches.

Zika virus (ZIKV) pandemic and its implication in congenital malformations and severe neurological disorders had created serious threats to global health. ZIKV is a mosquito-borne flavivirus which spread rapidly and infect a large number of people in a shorter time-span. Due to the lack of effective therapeutics, this had become paramount urgency to discover effective drug molecules to encounter the viral infection. Various anti-ZIKV drug discovery efforts during the past several years had been unsuccessful to develop an effective cure. The NS2B-NS3 protein was reported as an attractive therapeutic target for inhibiting viral proliferation, due to its central role in viral replication and maturation of non-structural viral proteins. Therefore, the current in silico drug exploration aimed to identify the novel inhibitors of Zika NS2B-NS3 protease by implementing an e-pharmacophore-based high-throughput virtual screening. A 3D e-pharmacophore model was generated based on the five-featured (ADPRR) pharmacophore hypothesis. Subsequently, the predicted model is further subjected to the high-throughput virtual screening to reveal top hit molecules from the various small molecule databases. Initial hits were examined in terms of binding free energies and ADME properties to identify the candidate hit exhibiting a favourable pharmacokinetic profile. Eventually, molecular dynamic (MD) simulations studies were conducted to evaluate the binding stability of the hit molecule inside the receptor cavity. The findings of the in silico analysis manifested affirmative evidence for three hit molecules with -64.28, -55.15 and -50.16 kcal/mol binding free energies, as potent inhibitors of Zika NS2B-NS3 protease. Hence, these molecules holds the promising potential to serve as a prospective candidates to design effective drugs against ZIKV and related viral infections.

Anti-inflammatory and anti-oxidant properties of Ipomoea nil (Linn.) Roth significantly alleviates cigarette smoke (CS)-induced acute lung injury via possibly inhibiting the NF-κB pathway.

Acute respiratory distress syndrome (ARDS), a serious manifestation of acute lung injury (ALI), is a debilitating inflammatory lung disease that is caused by multiple risk factors. One of the primary causes that can lead to ALI/ARDS is cigarette smoke (CS) and its primary mode of action is via oxidative stress. Despite extensive research, no appropriate therapy is currently available to treat ALI/ARDS, which means there is a dire need for new potential approaches. In our study we explored the protective effects of 70 % methanolic-aqueous extract of Ipomoea nil (Linn.) Roth, named as In.Mcx against CS-induced ALI mice models and RAW 264.7 macrophages because Ipomoea nil has traditionally been used to treat breathing irregularities. Male Swiss albino mice (20-25 ± 2 g) were subjected to CS for 10 uninterrupted days in order to establish CS-induced ALI murine models. Dexamethasone (1 mg/kg), In.Mcx (100 200, and 300 mg/kg) and normal saline (10 mL/kg) were given to respective animal groups, 1 h before CS-exposure. 24 h after the last CS exposure, the lungs and bronchoalveolar lavage fluid (BALF) of all euthanized mice were harvested. Altered alveolar integrity and elevated lung weight-coefficient, total inflammatory cells, oxidative stress, expression of pro-inflammatory cytokines (IL-1ß and IL-6) and chemokines (KC) were significantly decreased by In.Mcx in CS-exposed mice. In.Mcx also revealed significant lowering IL-1ß, IL-6 and KC expression in CSE (4 %)-activated RAW 264.7 macrophage. Additionally, In.Mcx showed marked enzyme inhibition activity against Acetylcholinesterase, Butyrylcholinesterase and Lipoxygenase. Importantly, In.Mcx dose-dependently and remarkably suppressed the CS-induced oxidative stress via not only reducing the MPO, TOS and MDA content but also improving TAC production in the lungs. Accordingly, HPLC analysis revealed the presence of many important antioxidant components. Finally, In.Mcx showed a marked decrease in the NF-κB expression both in in vivo and in vitro models. Our findings suggest that In.Mcx has positive therapeutic effects against CS-induced ALI via suppressing uncontrolled inflammatory response, oxidative stress, lipoxygenase and NF-κB p65 pathway.

Knowledge, attitude, and practice of pharmacists regarding asthma management: a cross-sectional study in Egypt.

BACKGROUND: Asthma is a significant public health issue that poses a substantial health and economic burden. Despite the availability of effective asthma medications, its management remain suboptimal. Recent asthma guidelines have highlighted the importance of pharmacist unique position and its interventional strategies in positively impacting asthma treatment outcomes. Therefore, this study aimed to assess the degree of Egyptian pharmacists' knowledge, attitudes, as well as their practices towards asthma management in line with the recent asthma guidelines. METHODS: This cross-sectional study was conducted among 800 pharmacists working in different private and governmental sectors. The data were collected using a 37-item pre-validated self-administered KAP questionnaire. The data were analyzed using Student's t-test and analysis of variance to assess the association between each KAP level and the sociodemographic variables at the significance level of 0.05. RESULTS: Of the 800 distributed questionnaire, a total of 550 participants (316 Male, and 234 Female) responded, representing a 68.7% response rate. The mean ± SD score of knowledge, attitude, practice, and barrier was 5.49 ± 1.65 (min = 0; max = 8), 23.5 ± 2.84 (min = 15, max = 30), 43.12 ± 8.61 (min = 28, max = 62), and 27.76 ± 3.72 (min = 17, max = 39), respectively. The results showed that poor knowledge, attitude, and practice scores were achieved by 30.54, 0, and 38.72% of participants, respectively. CONCLUSION: Our findings revealed the inconsistencies between poor pharmacists' knowledge and practices with respect to their positive attitudes. The lack of pharmacists' knowledge and compliance to recent GINA guidelines in this study highlight the crucial need for effective Educational strategies that should better equip pharmacists for their potential role in asthma care.

Maternal and birth cohort studies in the Gulf Cooperation Council countries: a systematic review and meta-analysis.

BACKGROUND: We systematically reviewed and chronicled exposures and outcomes measured in the maternal and birth cohort studies in the Gulf Cooperation Council (GCC) countries and quantitatively summarized the weighted effect estimates between maternal obesity and (1) cesarean section (CS) and (2) fetal macrosomia. METHODS: We searched MEDLINE-PubMed, Embase, Cochrane Library, Scopus, and Web of Science electronic databases up to 30 June 2019. We considered all maternal and birth cohort studies conducted in the six GCC countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates (UAE)). We categorized cohort studies on the basis of the exposure(s) (anthropometric, environmental, medical, maternal/reproductive, perinatal, or socioeconomic) and outcome(s) (maternal or birth) being measured. Adjusted weighted effect estimates, in the form of relative risks, between maternal obesity and CS and fetal macrosomia were generated using a random-effects model. RESULTS: Of 3502 citations, 81 published cohort studies were included. One cohort study was in Bahrain, eight in Kuwait, seven in Qatar, six in Oman, 52 in Saudi Arabia, and seven in the UAE. Majority of the exposures studied were maternal/reproductive (65.2%) or medical (39.5%). Birth and maternal outcomes were reported in 82.7% and in 74.1% of the cohort studies, respectively. In Saudi Arabia, babies born to obese women were at a higher risk of macrosomia (adjusted relative risk (aRR), 1.15; 95% confidence interval (CI), 1.10-1.20; I2 = 50%) or cesarean section (aRR, 1.21; 95% CI, 1.15-1.26; I2 = 62.0%). Several cohort studies were only descriptive without reporting the magnitude of the effect estimate between the assessed exposures and outcomes. CONCLUSIONS: Cohort studies in the GCC have predominantly focused on reproductive and medical exposures. Obese pregnant women are at an increased risk of undergoing CS delivery or macrosomic births. Longer-term studies that explore a wider range of environmental and biological exposures and outcomes relevant to the GCC region are needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017068910.

Maternal and birth cohort studies in the Gulf Cooperation Council countries: protocol for a systematic review and narrative evaluation.

INTRODUCTION: Cohort studies have revealed that genetic, socioeconomic, communicable and non-communicable diseases, and environmental exposures during pregnancy may influence the mother and her pregnancy, birth delivery and her offspring. Numerous studies have been conducted in the Gulf Cooperation Council (GCC) countries to examine maternal and birth health. The objectives of this protocol for a systematic review are to systematically review and characterise the exposures and outcomes that have been examined in the mother and birth cohort studies in the GCC region, and to summarise the strength of association between key maternal exposures during pregnancy (ie, body mass index) and different health-related outcomes (ie, mode of birth delivery). The review will then synthesise and characterise the consequent health implications and will serve as a platform to help identify areas that are overlooked, point out limitations of studies and provide recommendations for future cohort studies. METHODS AND ANALYSIS: Medline, Embase, Cochrane Library and Web of Science electronic databases will be comprehensively searched. Two reviewers will independently screen each study for eligibility, and where discrepancies arise they will be discussed and resolved; otherwise a third reviewer will be consulted. The two reviewers will also independently extract data into a predefined Excel spreadsheet. The included studies will be categorised on the basis of whether the participant is a mother, infant or mother-infant dyad. Outcome variables will be divided along two distinctions: mother or infant. Exposure variables will be divided into six domains: psychosocial, biological, environmental, medical/medical services, maternal/reproductive and perinatal/child. Studies are expected to be of heterogeneous nature; therefore, quantitative syntheses might be limited. ETHICS AND DISSEMINATION: There is no primary data collection; therefore, ethical review is not necessary. The findings of this review will be disseminated in a peer-reviewed journal and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42017068910.

Challenges and future directions in therapeutics for pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. The 5-year survival of < 5% has not changed in decades. In contrast to other major cancers, the incidence of PDAC is increasing. AREAS COVERED: The aims of this paper are first to analyze why PDAC is so difficult to treat and, second, to suggest future directions for PDAC therapeutics. The authors provide an article that is based on a comprehensive search through MEDLINE and the clinicalTrials.gov website. EXPERT OPINION: Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.