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1.
Proc Natl Acad Sci U S A ; 120(50): e2213020120, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38051772

ABSTRACT

Algorithms of social media platforms are often criticized for recommending ideologically congenial and radical content to their users. Despite these concerns, evidence on such filter bubbles and rabbit holes of radicalization is inconclusive. We conduct an audit of the platform using 100,000 sock puppets that allow us to systematically and at scale isolate the influence of the algorithm in recommendations. We test 1) whether recommended videos are congenial with regard to users' ideology, especially deeper in the watch trail and whether 2) recommendations deeper in the trail become progressively more extreme and come from problematic channels. We find that YouTube's algorithm recommends congenial content to its partisan users, although some moderate and cross-cutting exposure is possible and that congenial recommendations increase deeper in the trail for right-leaning users. We do not find meaningful increases in ideological extremity of recommendations deeper in the trail, yet we show that a growing proportion of recommendations comes from channels categorized as problematic (e.g., "IDW," "Alt-right," "Conspiracy," and "QAnon"), with this increase being most pronounced among the very-right users. Although the proportion of these problematic recommendations is low (max of 2.5%), they are still encountered by over 36.1% of users and up to 40% in the case of very-right users.

2.
Chem Biodivers ; : e202401021, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954767

ABSTRACT

α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-Vis., FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4 c (IC50=3.8 µM), 4 g (IC50=14.5 µM), and 4 f (IC50=17.1 µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4 f and 4 h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.

3.
Chem Biodivers ; : e202400305, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122648

ABSTRACT

Diabetes is an emerging threat to the world due to large number of deaths reported within the last decade. To overcome its spread and complications, herein, we reported synthesis and anti-diabetic potential of twelve novel 2-[(arylidene)methylidene]hydrazinyl-1,3-thiazole-5-carbaldehydes (3a-l). All compounds have shown good to excellent α-amylase inhibition activity, among them ortho substituted analogues, the compound 3a (IC50= 14.6 mM) and 3l (IC50= 17.9 mM) showed excellent inhibition potential due to their strong electron donating nature of the substituents attached at the aryl ring. The compounds 3a to 3h (IC50= 6.70-10.80 ppm) exhibited excellent anti-glycation potential as compared to standard amino-guanidine (IC50= 11.92 ppm). Almost all the tested compounds are found biocompatible and very safe to the human erythrocyte cells at all tested concentrations. The molecular docking results have found that the binding energy score of all the tested compounds against human serum albumin protein (pdb: 1AO6) is between -5.1827 to -6.8661 kcal/mol far better than standard amino-guanidine (-4.234 kcal/mol).

4.
J Pak Med Assoc ; 74(6): 1067-1073, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38948973

ABSTRACT

Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.


Subject(s)
Hyperprolactinemia , Prolactin , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/adverse effects , Female , Cross-Sectional Studies , Male , Hyperprolactinemia/epidemiology , Hyperprolactinemia/chemically induced , Hyperprolactinemia/blood , Hyperprolactinemia/drug therapy , Prolactin/blood , Adult , Middle Aged , Pakistan/epidemiology , Prevalence
5.
Ann Surg ; 278(5): 748-755, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37465950

ABSTRACT

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.


Subject(s)
Laparoscopy , Liver Failure , Liver Neoplasms , Humans , Hepatectomy/methods , Benchmarking , Postoperative Complications/etiology , Liver Neoplasms/surgery , Liver Neoplasms/etiology , Liver Failure/etiology , Laparoscopy/methods , Retrospective Studies , Length of Stay
6.
Horm Metab Res ; 55(3): 205-211, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36626934

ABSTRACT

Proton pump inhibitors (PPI) are commonly prescribed medications for a variety of gastrointestinal disorders around the globe. Long-term utilization of proton pump inhibitors is linked with different adverse events. Although, short-term therapy has been demonstrated to have little or no impact on endocrine hormones in men, yet its safety with long-term use has poorly been studied. We aimed to evaluate the impacts of long-term utilization of proton pump inhibitors on male reproductive hormones and its clinical outcomes. A cross-sectional study was performed in two out-patients gastroenterology clinics in Khyber Pakhtunkhwa province. Male patients who were using PPIs regularly for≥3 months were enrolled in this study. Among 65 enrolled participants, patients with sexual complaints have significant variations in mean serum levels of prolactin (p<0.001), sex hormone binding globulins (p=0.043), total testosterone (p<0.001) and progesterone (p=0.001) as compared to patients without sexual complaints. Significantly high values of prolactin mean ranks were observed in patient with sexual complaints (p<0.001). There were statistically significant correlations of serum levels of sex hormone binding globulins (p=0.003), total testosterone (p=0.008) and progesterone (p<0.001) with serum prolactin levels. Similarly, statistically significant variation was observed for decreased libido (p=0.001), erectile dysfunction (p=0.001) and decreased semen mass ((p<0.001) between normal and hyperprolactinemic PPI users. Highly significant differences were observed in serum sex hormone binding globulins (p<0.001), total testosterone (p<0.001) and progesterone (p<0.001) values in normal and hyperprolactinemic groups. In conclusion, long-term utilization of PPI may induce endocrine hormone disruption with subsequent sexual complications.


Subject(s)
Globulins , Prolactin , Humans , Male , Proton Pump Inhibitors/adverse effects , Progesterone , Cross-Sectional Studies , Testosterone
7.
Chem Biodivers ; 20(5): e202201134, 2023 May.
Article in English | MEDLINE | ID: mdl-37052518

ABSTRACT

The molecular hybrid approach is very significant to combat various drug-resistant disorders. A simple, convenient, and cost-effective synthesis of thiazole-based chalcones is accomplished, using a molecular hybrid approach, in two steps. The compound 1-(2-phenylthiazol-4-yl)ethanone (3) was used as the main intermediate for the synthesis of 3-(arylidene)-1-(2-phenylthiazol-4-yl)prop-2-en-1-ones (4a-f). Thin layer chromatography was used to testify the formation and purity of all synthesized compounds. Further structural confirmation of all compounds was achieved via different spectroscopic techniques (UV, FT-IR, 1 H- and 13 C-NMR) and elemental analysis. All synthesized compounds were tested for their α-amylase inhibition and antioxidant potential. The cytotoxic property of compounds was also tested with in vitro haemolytic assay. All tested compounds showed moderate to excellent α-amylase inhibition and antioxidant activity. All tested compounds are found safe to use due to their less toxicity when compared to the standard Triton X. The molecular docking simulation study of all synthesized compounds was also conducted to examine the best binding interactions with human pancreatic α-amylase (pdb: 4 W93) using AutodockVina. The molecular docking results authenticated the in vitro amylase inhibition results, i.e., 3-(3-Methoxyphenyl)-1-(2-phenylthiazol-4-yl)prop-2-en-1-one (4e) exhibited lowest IC50 value 54.09±0.11  µM with a binding energy of -7.898 kcal/mol.


Subject(s)
Chalcone , Chalcones , Humans , Structure-Activity Relationship , Antioxidants/pharmacology , Chalcones/chemistry , Molecular Docking Simulation , alpha-Amylases , Thiazoles/chemistry , Spectroscopy, Fourier Transform Infrared
8.
Molecules ; 28(11)2023 May 26.
Article in English | MEDLINE | ID: mdl-37298842

ABSTRACT

The Corey-Seebach reagent plays an important role in organic synthesis because of its broad synthetic applications. The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium. A large variety of natural products (alkaloids, terpenoids, and polyketides) can be accessed successfully by utilizing this reagent. This review article focuses on the recent contributions (post-2006) of the Corey-Seebach reagent towards the total synthesis of natural products such as alkaloids (lycoplanine A, diterpenoid alkaloids, etc.), terpenoids (bisnorditerpene, totarol, etc.), polyketide (ambruticin J, biakamides, etc.), and heterocycles such as rodocaine and substituted pyridines, as well and their applications towards important organic synthesis.


Subject(s)
Alkaloids , Biological Products , Polyketides , Indicators and Reagents , Terpenes
9.
J Pak Med Assoc ; 73(3): 671-673, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36932779

ABSTRACT

Laparoscopic cholecystectomy (LC) is commonly performed for benign gallbladder diseases. Biliary leak is the most common complication of bile duct injury following this surgery. We report a case of persistent bile leak following the procedure despite endoscopic and radiological management. A female patient presented to the hepatopancreatobiliary unit of the Bahria International Hospital (Orchard), Lahore, with complaint of persistent bile leakage after laparoscopic cholecystectomy performed elsewhere. She had been investigated in various hospitals but the cause of the persistent bile leak remained a mystery and she was offered surgery. After real time fluoroscopic contrast enhanced imaging, further confirmed by a Computerised Tomography (CT) Scan of the abdomen, it was revealed that the persistent bile leak in the drain was due to iatrogenic injury of the duodenum secondary to percutaneous catheter insertion. The patient was managed non-surgically. She remained stable. This is a rare complication of one of the most common surgical procedures performed in the world.


Subject(s)
Bile , Cholecystectomy, Laparoscopic , Humans , Female , Cholecystectomy/adverse effects , Cholecystectomy, Laparoscopic/adverse effects , Bile Ducts/diagnostic imaging , Bile Ducts/surgery , Bile Ducts/injuries , Cholangiopancreatography, Endoscopic Retrograde/methods
10.
Clin Gerontol ; 46(4): 511-524, 2023.
Article in English | MEDLINE | ID: mdl-35672952

ABSTRACT

OBJECTIVES: Decline in language and cognitive functioning often deprives people living with moderate-to-severe dementia of self-reporting their quality of life (QoL) on the written and verbal formats of questionnaires. This systematic review aimed to evaluate the effectiveness of pictorial tools as an alternative method for enabling people living with dementia to self-report their QoL. METHODS: PubMed, PsycINFO, CINAHL, and EMBASE were searched. Primary research studies reporting on information elicitation from people living with dementia through pictures were deemed eligible. Six studies satisfied the inclusion criteria. Methodological quality of the studies was evaluated through Downs and Black checklist. Data was extracted according to population, intervention, comparator, and outcomes (PICO) and results were summarized and supplemented by narrative synthesis. RESULTS: Compared to usual communication methods, pictorial tools were found to have a superior effect on comprehension of conversations and decision-making abilities, minimal effect on preference consistency, and an undeterminable effect on discourse features. CONCLUSIONS: There is consistent evidence that pictures enhance comprehension and might facilitate decision-making abilities. CLINICAL IMPLICATIONS: QoL information can be elicited more effectively through pictorial tools. Future studies warrant development of pictorial versions of standardized QoL tools which will assist the inclusion of people living with severe dementia.


Subject(s)
Dementia , Quality of Life , Humans , Cognition , Communication , Language
11.
Planta ; 256(6): 111, 2022 Nov 09.
Article in English | MEDLINE | ID: mdl-36352050

ABSTRACT

MAIN CONCLUSION: Allele-specific expressed genes (ASEGs) are widespread in maize hybrid lines and play important roles of complementation of biological pathways in heterosis. Heterosis (hybrid vigor) is an important phenomenon with both theoretical and practical value. However, our understanding of the genetic and molecular mechanisms behind heterosis is still limited. Here, we analyzed a comprehensive dataset of maize (Zea mays L.), including RNA-seq data from three hybrid-parent triplets (HPTs) and acetylated protein data from one HPT. The gene expression patterns exhibited extensive variation between the hybrids and their parents, and a substantial number of allele-specific expressed genes (ASEGs) were identified in the hybrids. Notably, ASEGs from different HPTs were significantly enriched in various conserved pathways. The parental alleles of ASEGs with fewer deleterious single-nucleotide polymorphisms were more likely to be expressed in hybrid lines than other parental alleles. ASEGs were mainly enriched in the functional gene ontology terms protein biosynthesis, photosynthesis, and metabolism. In addition, the ASEGs across the three HPTs were involved in key photosynthetic pathways and might enhance the photosynthetic efficiency of the hybrids. These findings suggest that ASEGs involved in complementary biological pathways in maize hybrids contribute to heterosis, shedding new light on the molecular mechanism of heterosis.


Subject(s)
Hybrid Vigor , Zea mays , Hybrid Vigor/genetics , Zea mays/genetics , Gene Expression Regulation, Plant , Hybridization, Genetic , Alleles
12.
Crit Care ; 26(1): 209, 2022 07 11.
Article in English | MEDLINE | ID: mdl-35818054

ABSTRACT

BACKGROUND: In response to the COVID-19 pandemic, concerted efforts were made by provincial and federal governments to invest in critical care infrastructure and medical equipment to bridge the gap of resource-limitation in intensive care units (ICUs) across Pakistan. An initial step in creating a plan toward strengthening Pakistan's baseline critical care capacity was to carry out a needs-assessment within the country to assess gaps and devise strategies for improving the quality of critical care facilities. METHODS: To assess the baseline critical care capacity of Pakistan, we conducted a series of cross-sectional surveys of hospitals providing COVID-19 care across the country. These hospitals were pre-identified by the Health Services Academy (HSA), Pakistan. Surveys were administered via telephonic and on-site interviews and based on a unique checklist for assessing critical care units which was created from the Partners in Health 4S Framework, which is: Space, Staff, Stuff, and Systems. These components were scored, weighted equally, and then ranked into quartiles. RESULTS: A total of 106 hospitals were surveyed, with the majority being in the public sector (71.7%) and in the metropolitan setting (56.6%). We found infrastructure, staffing, and systems lacking as only 19.8% of hospitals had negative pressure rooms and 44.4% had quarantine facilities for staff. Merely 36.8% of hospitals employed accredited intensivists and 54.8% of hospitals maintained an ideal nurse-to-patient ratio. 31.1% of hospitals did not have a staffing model, while 37.7% of hospitals did not have surge policies. On Chi-square analysis, statistically significant differences (p < 0.05) were noted between public and private sectors along with metropolitan versus rural settings in various elements. Almost all ranks showed significant disparity between public-private and metropolitan-rural settings, with private and metropolitan hospitals having a greater proportion in the 1st rank, while public and rural hospitals had a greater proportion in the lower ranks. CONCLUSION: Pakistan has an underdeveloped critical care network with significant inequity between public-private and metropolitan-rural strata. We hope for future resource allocation and capacity development projects for critical care in order to reduce these disparities.


Subject(s)
COVID-19 , Pandemics , Adult , Critical Care , Cross-Sectional Studies , Humans , Pakistan
13.
Environ Res ; 215(Pt 1): 114241, 2022 12.
Article in English | MEDLINE | ID: mdl-36100100

ABSTRACT

This study is based on the removal of methylene blue (MB) from aqueous solution by cost effective and biodegradable adsorbent carboxymethyl starch grafted polyvinyl pyrolidone (Car-St-g-PVP). The Car-St-g-PVP was synthesized by grafting vinyl pyrolidone onto carboxymethyl starch by free radical polymerization reaction. The structure and different properties of Car-St-g-PVP were determined by 1H NMR, FT-IR, XRD, TGA and SEM. A series of batch experiments were conducted for the removal of MB, The adsorption affecting factors such as temperature, contact time, initial concentration of MB dye, dose of Car-St-g-PVP and pH were studied in detail. The other parameters like the thermodynamic study, kinetics and isothermal models were fitted to the experimental data. The results showed that pseudo 2nd order kinetics and Langmuir's adsorption isotherms were best fitted to experimental data with regression coefficient R2 viz. 0.99 and 0.97. The kinetic study showed that the adsorption mechanism favored chemisorption. The Gibbs free energy (ΔG°) for the adsorption process was found to be -7.31 kJ/mol, -8.23 kJ/mol, -9.00 kJ/mol and -10.10 kJ/mol at 25 °C, 35 °C, 45 °C and 55 °C respectively. The negative values of ΔG° suggested the spontaneous nature of the adsorption process. Similarly, the positive values of entropy (ΔS°) and enthalpy (ΔH°) 91.27 J/k.mol and 19.90 kJ/mol showed the increasing randomness and endothermic nature of the adsorption process. The value of separation factor (RL) was found to be less than one (RL < 1), which supported the feasibility of the adsorption process. The maximum MB removal percentage (% R) was found to be 98.6%. So, these findings show that Car-St-g-PVP can be meritoriously used for the treatment of MB from wastewater.


Subject(s)
Methylene Blue , Water Pollutants, Chemical , Adsorption , Carboxylic Acids , Hydrogen-Ion Concentration , Kinetics , Methylene Blue/chemistry , Polyvinyls , Povidone , Spectroscopy, Fourier Transform Infrared , Starch , Thermodynamics , Wastewater
14.
Biotechnol Appl Biochem ; 69(6): 2624-2640, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35048414

ABSTRACT

Thidiazuron (TDZ) is an active substituted phenyl urea compound that has found a significant role as a plant growth regulator. The most exciting aspect of its function is that it can mimic auxins and cytokinin but is chemically different from these two. Many theories have been put forward, and experiments performed to understand the mode of action of TDZ in callogenesis. One suggested mechanism presents that it works by inhibiting the cytokinin degrading enzymes that compete with cytokinin for an active site on the enzyme. An example is the TDZ-induced suppressed expression of gibberellic acid (GA) biosynthesis genes encoding GA3 and GA20 oxidases. This is entailed with a slightly increased expression of GA catabolism genes encoding GA20 oxidase. Similarly, one of the recommendations is that TDZ induces the expression of specific genes and transcription regulatory sequences that are either responsible directly for callus formation or in turn induce other auxins or cytokinin for callogenesis. There is no concise review available that discusses the details of TDZ-induced callus, specifically and other in vitro cultures in general. This review is an attempt to explore all these pathways and mechanisms involved in callogenesis in plants stimulated by TDZ.


Subject(s)
Cytokinins , Plant Growth Regulators , Plant Growth Regulators/pharmacology , Cytokinins/pharmacology , Cytokinins/metabolism , Plants/metabolism , Oxidoreductases , Indoleacetic Acids
15.
Hum Resour Health ; 19(Suppl 1): 120, 2022 01 28.
Article in English | MEDLINE | ID: mdl-35090470

ABSTRACT

BACKGROUND: Globally the occurrence of disasters has increased more than fourfold during the last three decades. The main concern for the healthcare system responding to a disaster is its ability to deal with the sudden influx of patients and maintaining a certain level of surge capacity. Health workers are considered to be the major driving force behind any health system. Their role gets even more prominent during disasters or public health emergencies. With the lack of information on the health workforce in the tertiary healthcare system of Khyber Pakhtunkhwa, where most of the disaster surge is diverted, it is difficult to plan and respond to accommodate the sudden surge of patients. METHODS: This was a mixed method cross-sectional survey conducted in all the tertiary care hospitals of Khyber Pakhtunkhwa province of Pakistan to assess the current staffing situation and surge capacity based on the current workload. Annual service statistics of 2018 were collected from all the tertiary care hospitals of the province. WISN was piloted with only one healthcare staff category, i.e., for doctors in Ayub Teaching Hospital before assessment in all the tertiary care hospitals was undertaken. RESULTS: Overall, there were 1215 surplus doctors in medical and allied specialties and 861 doctors in surgical and allied specialties in the tertiary healthcare system. The health care system has an acute shortage of 565 emergency department doctors. The tertiary healthcare system of KP has an overall shortage of 1099 nurses. Based on the WISN generated numbers for doctors, the tertiary care system of KP has a combined healthcare staff (doctors and nurses) that can manage an additional surge of 6.3% of patients with the current patient workload. CONCLUSION: The tertiary health care system of the Khyber Pakhtunkhwa Province of Pakistan does not possess the required ≥ 20% HR surge capacity indicating that the tertiary healthcare system is poorly prepared for disasters or public health emergencies. The lack of nursing staff, more than the doctors, is the major reason behind the lack of HR surge capacity of the tertiary health care system.


Subject(s)
Surge Capacity , Workload , Cross-Sectional Studies , Humans , Pakistan , Tertiary Healthcare , Workforce
16.
Endocr Regul ; 56(2): 134-147, 2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35489049

ABSTRACT

Proton pump inhibitors (PPIs) are the most widely prescribed medications in the world. According to numerous studies, PPIs have been linked to hyperprolactinemia, which can lead to a variety of sexual and reproductive issues. This review summarizes the effects of numerous PPIs on the blood prolactin levels and associated sexual dysfunctions, which have an effect on the patient's life quality and fertility. The study is taken into account all the available resources till January 31, 2021. Out of total 364, only 27 relevant resources were involved in this review. In certain studies, short-term PPIs use has been shown to have little or no effect on the blood prolactin and other reproductive hormones levels. PPIs have been linked to the development of hyperprolactinemia in several case studies with varying degrees of the blood prolactin levels increase seen in individuals taking PPI alone or in combination with medications, like prokinetics. The relative risk of the sexual consequences development, such as gynecomastia, has been documented using lansoprazole and omeprazole in various cohort studies. On the other hand, other bits of data are insufficient to establish a definite relationship that can turn a possibility into certainty. The majority of the literature data is comprising of double-blind, randomized, crossover studies, case reports, and adverse drug reaction incidents reported to various pharmacovigilance centers. To investigate this link, high-quality studies in patients taking PPIs for a longer time period are needed. We conclude this article with a comprehensive discussion of the hyperprolactinemia clinical implications and the PPIs' function.


Subject(s)
Hyperprolactinemia , Proton Pump Inhibitors , Humans , Hyperprolactinemia/chemically induced , Hyperprolactinemia/drug therapy , Male , Prolactin , Proton Pump Inhibitors/adverse effects , Randomized Controlled Trials as Topic
17.
Chem Biodivers ; 19(11): e202200824, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36193667

ABSTRACT

Thiazole has been a key scaffold in antidiabetic drugs. In quest of new and more effective drugs a simple, efficient, high yielding (67-79 %) and convenient synthesis of arylidenehydrazinyl-4-methoxyphenyl)thiazoles is accomplished over two steps. The synthesis involved the condensation of aryl substituted thiosemicarbazones and 2-bromo-4-methoxyacetophenone in absolute ethanol. The structures of the resulting thiazoles are in accord with their UV/VIS, FT-IR, 1 H-, 13 C-NMR and HRMS data. All compounds were evaluated for alpha(α)-amylase inhibition potential, antiglycation, antioxidant abilities and biocompatibility. The compounds library identified 2-(2-(3,4-dichlorobenzylidene)hydrazinyl)-4-(4-methoxyphenyl)thiazole as a lead molecule against α-amylase inhibition with an IC50 of 5.75±0.02 µM. α-Amylase inhibition is also supported by molecular docking studies against α-amylase. All the obtained thiazoles also showed promising antiglycation activity with 4-(4-methoxyphenyl)-2-{2-[2-(trifluoromethyl)benzylidene]hydrazinyl}thiazole exhibiting the best inhibition (IC50 = 0.383±0.001 mg/mL) compared to control. The tested compounds are also biocompatible at the concentration used i. e., 10 µM.


Subject(s)
Diabetes Complications , Diabetes Mellitus, Type 2 , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Diabetes Mellitus, Type 2/drug therapy , Spectroscopy, Fourier Transform Infrared , alpha-Amylases , Thiazoles/chemistry , Molecular Structure
18.
Chem Biodivers ; 19(2): e202100581, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34875137

ABSTRACT

Ethyl 2-(2-arylidene-1-alkylhydrazinyl)thiazole-4-carboxylates (1a-k) were synthesized by alkylation on HN- of ethyl 2-(2-arylidenehydrazinyl)thiazole-4-carboxylates. The proposed structures (1a-k) are corroborated by spectro-analytical techniques like UV, FT-IR, 1 H-, 13 C-NMR and HR-MS. All synthesized compounds were screened for their antiglycation and antioxidant assays. The in vitro antiglycation results revealed promising activity of compounds 1a, 1b, 1d, 1e, 1f, 1g, 1j and 1k with IC50 values 0.0004±1.097-17.22±0.538 µM when compared to standard, aminoguanidine (IC50 =25.50±0.337 µM). Among all tested compounds 1j and 1k are the best antiglycating agents with IC50 values 1.848±0.646 and 0.0004±1.097 µM, respectively. The in-silico studies also agree with these results where binding energy for 1j and 1k was found to be -9.25 and -8.42 kcal/mol with calculated dissociation constants of 0.16 and 0.67 µM, respectively. The antiglycation results demonstrate the application of these compounds in reducing diabetic complications.


Subject(s)
Antineoplastic Agents , Thiazoles , Antineoplastic Agents/pharmacology , Molecular Docking Simulation , Spectroscopy, Fourier Transform Infrared , Structure-Activity Relationship , Thiazoles/chemistry
19.
Int J Mol Sci ; 23(11)2022 May 25.
Article in English | MEDLINE | ID: mdl-35682602

ABSTRACT

RNA-binding proteins (RBPs) form complex interactions with RNA to regulate the cell's activities including cell development and disease resistance. RNA-binding proteome (RBPome) aims to profile and characterize the RNAs and proteins that interact with each other to carry out biological functions. Generally, RNA-centric and protein-centric ribonomic approaches have been successfully developed to profile RBPome in different organisms including plants and animals. Further, more and more novel methods that were firstly devised and applied in mammalians have shown great potential to unravel RBPome in plants such as RNA-interactome capture (RIC) and orthogonal organic phase separation (OOPS). Despise the development of various robust and state-of-the-art ribonomics techniques, genome-wide RBP identifications and characterizations in plants are relatively fewer than those in other eukaryotes, indicating that ribonomics techniques have great opportunities in unraveling and characterizing the RNA-protein interactions in plant species. Here, we review all the available approaches for analyzing RBPs in living organisms. Additionally, we summarize the transcriptome-wide approaches to characterize both the coding and non-coding RBPs in plants and the promising use of RBPome for booming agriculture.


Subject(s)
Eukaryota , RNA , Animals , Eukaryota/genetics , Mammals/metabolism , Plants/genetics , Plants/metabolism , Proteome/metabolism , RNA/metabolism , RNA-Binding Proteins/metabolism , Transcriptome
20.
Molecules ; 27(11)2022 May 24.
Article in English | MEDLINE | ID: mdl-35684312

ABSTRACT

Currently, the growth and yield of crops are restrained due to an increase in the occurrence of ecological stresses globally. Biogenic generation of nanomaterials is an important step in the development of environmentally friendly procedures in the nanotechnology field. Silver-based nanomaterials are significant because of their physical, chemical, and biological features along with their plentiful applications. In addition to useful microbes, the green synthesized Ag nanomaterials are considered to be an ecologically friendly and environmentally biocompatible method for the enhancement of crop yield by easing stresses. In the recent decade, due to regular droughts, infrequent precipitation, salinity, and increased temperature, the climate alternation has changed certain ecological systems. As a result of these environmental changes, crop yield has decreased worldwide. The role of biogenic Ag nanomaterials in enhancing methylglyoxal detoxification, antioxidant defense mechanisms, and generating tolerance to stresses-induced ROS injury has been methodically explained in plants over the past ten years. However, certain studies regarding stress tolerance and metal-based nanomaterials have been directed, but the particulars of silver nanomaterials arbitrated stresses tolerance have not been well-reviewed. Henceforth, there is a need to have a good understanding of plant responses during stressful conditions and to practice the combined literature to enhance tolerance for crops by utilization of Ag nanoparticles. This review article illustrates the mechanistic approach that biogenic Ag nanomaterials in plants adopt to alleviate stresses. Moreover, we have appraised the most significant activities by exogenous use of Ag nanomaterials for improving plant tolerance to salt, low and high temperature, and drought stresses.


Subject(s)
Metal Nanoparticles , Silver , Crops, Agricultural , Droughts , Salinity , Stress, Physiological/physiology
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