Polycystic ovary syndrome: A disorder of reproductive age, its pathogenesis, and a discussion on the emerging role of herbal remedies

Polycystic ovary syndrome (PCOS) is a very common, complex, and heterogeneous endocrine disorder of women that involves a combination of environmental and genetic factors. PCOS affects women of growing age particularly at the early to late reproductive stage (15-35 years). Currently, PCOS affects 1 in every 10 women worldwide. It is characterized majorly by a raised level of androgens such as testosterone and a large number of ovarian cysts (more than 10) that cause anovulation, infertility, and irregular menstrual cycle. PCOS is also related to other endocrine and metabolic abnormalities, such as obesity, hirsutism, acne, diabetes, insulin resistance, and glucose impairment. PCOS can be treated with allopathic, ayurvedic, and natural or herbal medications along with lifestyle modifications. Herbal medicines remained in demand for numerous reasons such as high cost and side effects associated with the use of allopathic medicine and our traditional norms, which have helped humans to use more herbal products for their health benefits. Estrogenic and nonestrogenic phytochemicals present in various plant species such as Glycyrrhiza glabra L. [Fabaceae], Aloe vera (L.) Burm. f. [Asphodelaceae], Silybum marianum (L.). Gaertn. [Asteraceae], Serenoa repens (W.Bartram) Small [Arecaceae], Actaea racemosa L. [Ranunculaceae], and Angelica sinensis (Oliv.) Diels [Apiaceae] are effective and harmless. Herbal medicines are found to be cost-effective, efficacious, and a highly esteemed source of management/treatment for PCOS than allopathic medicines. In this literature review, diagnosis, signs, and symptoms of PCOS; causes of hormonal imbalance; and risk factors associated with PCOS and their management are discussed briefly, and the focus was to find out the role of herbal remedies in PCOS management

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-1β and IL-6) and chemokines (KC) were significantly decreased by In.Mcx in CS-exposed mice. In.Mcx also revealed significant lowering IL-1β, 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

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-KB 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 weightcoefficient, total inflammatory cells, oxidative stress, expression of pro-inflammatory cytokines (IL-10 and IL-6) and chemokines (KC) were significantly decreased by In.Mcx in CS-exposed mice. In.Mcx also revealed significant lowering IL-10, 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-KB 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-KB p65 pathway

Carbapenem- and colistin-resistant Enterobacterales in intensive care unit patients in Mediterranean countries, 2019

IntroductionThe colonization of patients by carbapenemase-producing Enterobacterales (CPE) has been associated with heightened mortality, especially in vulnerable individuals within intensive care units (ICUs). Our study aimed to comprehensively assess CPE prevalence among ICU patients across the Mediterranean region pre-COVID-19, conducting a multicenter prevalence study in the first quarter of 2019.MethodsWe collected clinical data and rectal or fecal samples from 256 ICU patients for CPE testing. Additionally, we performed whole-genome sequencing on 40 representative CPE strains to document their molecular characteristics.ResultsAmong the 256 patients, CPE was detected in 73 samples (28.5%), with prevalence varying from 3.3 to 69.0% across participating centers. We observed 13 colistin-resistant CPE strains, affecting three ICUs. Genetic analysis revealed highly diverse E. coli and K. pneumoniae strains, predominantly from international high-risk clones. Notably, blaOXA-48 and blaNDM-1 were the most prevalent carbapenemase genes. Molecular typing uncovered potential patient clusters in six centers. Significantly, longer hospital stays were associated with increased CPE carriage (p < 0.001). Nine centers across Morocco, Tunisia, Egypt, and Lebanon voluntarily participated.DiscussionOur study provides CPE prevalence in Mediterranean ICUs and reaffirms established CPE presence in this setting but also provides updates on the molecular diversity of CPE strains. These findings highlight the imperative of reinforcing infection control measures in the participating ICUs to curtail escalated mortality rates, and of strictly applying isolation measures around patients originating from the Mediterranean region when transferred to other healthcare institutions

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

Therapeutic potential of hydroxychloroquine on serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) in rheumatoid arthritis patients

Objective: To assess the serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) level in rheumatoid arthritis (RA) patients in view of different treatment regimens received and evaluate its relation with disease activity. Patients and methods: Ninety female RA patients were included. Sixty were on disease modifying anti-rheumatic drugs (DMARDs); 34 on hydroxychloroquine (HCQ) plus methotrexate (MTX), 26 on leflunomide (LFN) plus MTX and 30 newly diagnosed cases not yet on any treatment. Thirty age and gender matched healthy subjects served as controls. Full history taking, clinical examination and relevant laboratory investigations were performed. Disease activity score, in 28 joints (DAS-28), was calculated. Results: Serum BAFF level was significantly higher in patients (1.82 ± 0.91 ng/ml) compared to control (0.71 ± 0.33 ng/ml; p < 0.001). There was a significantly lower BAFF and disease activity in patients receiving DMARDs (1.55 ± 0.73 ng/ml and 3.08 ± 0.73) compared to new cases (2.36 ± 1.02 ng/ml and 3.46 ± 0.82) (p < 0.001 and p = 0.036, respectively). Those receiving HCQ + MTX had a lower BAFF level (1.29 ± 0.51 ng/ml) compared to those receiving LFN + MTX (1.94 ± 0.85 ng/ml; p = 0.002). The BAFF level significantly correlated with the presence of anti-CCP antibodies, DAS28 and MTX dose in all RA patients (r = 0.24, p = 0.02; r = 0.504, p < 0.001; r = 0.51, p < 0.001, respectively). Only DAS28 and MTX dose would highly influence the BAFF level (p = 0.015 and p = 0.001, respectively). Conclusion: Elevated level of BAFF in RA has been confirmed with a notable relation to disease activity making it a promising marker. The beneficial effect of hydroxychloroquine in dampening BAFF level throws light on the importance of considering it in combination among the newly developed biologics that also target B-cells

Poloxamer-188 and d-α-tocopheryl polyethylene glycol succinate (TPGS-1000) mixed micelles integrated orodispersible sublingual films to improve oral bioavailability of ebastine in vitro and in vivo characterization

Orodispersible sublingual films (OSFs) composed of hydrophilic polymers were loaded with poloxamer-188 and d-alpha-tocopheryl polyethylene glycol succinate (TPGS-1000) mixed micelles to improve the oral bioavailability of a poorly soluble drug, ebastine (EBT). Mixed micelles formed by thin-film hydration method were incorporated into orodispersible sublingual film, consisting of HPMC and glycerol, using solvent casting technique. The mixed micelles and films were thoroughly evaluated for physicochemical characterization (size, polydispersity index, zeta potential, entrapment efficiency, thickness, weight, surface pH studies, disintegration time, swelling indices, mechanical properties, FTIR, PXRD, DSC, SEM, AFM, in vitro drug release, in vivo bioavailability, and toxicological studies). The results showed that the average particle size of mixed micelles was 73 nm. The mean zeta potential and PDI of the optimal mixed micelles formulation were -26 mV and 0.16, respectively. Furthermore, the maximum entrapment efficiency 82% was attained. The film's disintegration time was in the range of 28 to 102 s in aqueous media. The integrity of micelles was not affected upon incorporation in films. Importantly, the micelles-loaded films revealed rapid absorption, high permeability, and increased bioavailability of EBT as compared to the pure drug. The existence of ebastine loaded mixed micelles in the films enhanced the bioavailability about 2.18 folds as compared to pure drug. Further, the results evidently established in-vitro and in-vivo performance of bioavailability enhancement, biocompatibility, and good safety profile of micelles-loaded orodispersible EBT films. Finally, it was concluded that film loaded with poloxamer-188/TPGS-1000 mixed micelles could be an effective carrier system for enhancing the bioavailability of ebastine.Apsis Pharmaceutical, Gujranwala, Pakista

Formulation and evaluation of Ketoconazole polymeric films for topical application

The objective of the current paper was to prepare and evaluate various polymeric films for fungal infection treatment and its impact on volunteer patients. Different Eudragit polymeric films containing Ketoconazole as antifungal drug were prepared by solvent casting technique. The prepared films were tested for their physico-mechanical properties as tensile strength, physical endurance, elasticity, water vapor permeation and water loss. The release of ketoconazole from the prepared medicated films was examined. It is involved 20 volunteers suffering from legs fungal infection. Ten of the patients used the films and a follow up study was carried out for 14 days, in comparison with other patients who applied ketoconazole medicated ointment, cream gel and Emulgel. The results revealed that films prepared with Eudragit RL 100 containing glyceryl triacetate produced maximum release of ketoconazole both In vitro and In vivo as compared with other topical dosage forms as ointment, cream, gel and Emulgel. Moreover, the films constitute a simple and convenient method for treatment of various fungal infections. As conclusion, the use of antifungal drugs such as Ketoconazole incorporated in polymeric films, the output results provided promised evidence in the treatment of dermatophytosi

Hedgehog signaling: Linking embryonic lung development and asthmatic airway remodeling

The development of the embryonic lung demands complex endodermal-mesodermal interactions, which are regulated by a variety of signaling proteins. Hedgehog (Hh) signaling is vital for lung development. It plays a key regulatory role during several morphogenic mechanisms, such as cell growth, differentiation, migration, and persistence of cells. On the other hand, abnormal expression or loss of regulation of Hh signaling leads to airway asthmatic remodeling, which is characterized by cellular matrix modification in the respiratory system, goblet cell hyperplasia, deposition of collagen, epithelial cell apoptosis, proliferation, and activation of fibroblasts. Hh also targets some of the pathogens and seems to have a significant function in tissue repairment and immune-related disorders. Similarly, aberrant Hh signaling expression is critically associated with the etiology of a variety of other airway lung diseases, mainly, bronchial or tissue fibrosis, lung cancer, and pulmonary arterial hypertension, suggesting that controlled regulation of Hh signaling is crucial to retain healthy lung functioning. Moreover, shreds of evidence imply that the Hh signaling pathway links to lung organogenesis and asthmatic airway remodeling. Here, we compiled all up-to-date investigations linked with the role of Hh signaling in the development of lungs as well as the attribution of Hh signaling in impairment of lung expansion, airway remodeling, and immune response. In addition, we included all current investigational and therapeutic approaches to treat airway asthmatic remodeling and immune system pathway diseases.National Natural Science Foundation of China (NSFC

Data_Sheet_1_Carbapenem- and colistin-resistant Enterobacterales in intensive care unit patients in Mediterranean countries, 2019.zip

IntroductionThe colonization of patients by carbapenemase-producing Enterobacterales (CPE) has been associated with heightened mortality, especially in vulnerable individuals within intensive care units (ICUs). Our study aimed to comprehensively assess CPE prevalence among ICU patients across the Mediterranean region pre-COVID-19, conducting a multicenter prevalence study in the first quarter of 2019.MethodsWe collected clinical data and rectal or fecal samples from 256 ICU patients for CPE testing. Additionally, we performed whole-genome sequencing on 40 representative CPE strains to document their molecular characteristics.ResultsAmong the 256 patients, CPE was detected in 73 samples (28.5%), with prevalence varying from 3.3 to 69.0% across participating centers. We observed 13 colistin-resistant CPE strains, affecting three ICUs. Genetic analysis revealed highly diverse E. coli and K. pneumoniae strains, predominantly from international high-risk clones. Notably, blaOXA-48 and blaNDM-1 were the most prevalent carbapenemase genes. Molecular typing uncovered potential patient clusters in six centers. Significantly, longer hospital stays were associated with increased CPE carriage (p DiscussionOur study provides CPE prevalence in Mediterranean ICUs and reaffirms established CPE presence in this setting but also provides updates on the molecular diversity of CPE strains. These findings highlight the imperative of reinforcing infection control measures in the participating ICUs to curtail escalated mortality rates, and of strictly applying isolation measures around patients originating from the Mediterranean region when transferred to other healthcare institutions.</p