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1.
J Enzyme Inhib Med Chem ; 39(1): 2311818, 2024 Dec.
Article En | MEDLINE | ID: mdl-38488131

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.


Antineoplastic Agents , Topoisomerase II Inhibitors , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/chemistry , Structure-Activity Relationship , Intercalating Agents/pharmacology , Thiones/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Imidazoles/pharmacology , DNA , Apoptosis , Molecular Docking Simulation , DNA Topoisomerases, Type II/metabolism , Cell Proliferation
2.
J Biomol Struct Dyn ; : 1-21, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38517058

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase. Despite advancements in tyrosine kinase inhibitors, challenges such as efficacy, safety concerns, and recurring drug resistance persist. This study aims to discover potential c-Abl kinase inhibitors from plant compounds with anti-leukemic properties, employing drug-likeness assessment, molecular docking, in silico pharmacokinetics (ADMET) screening, density function theory (DFT), and molecular dynamics simulations (MDS). Out of 58 screened compounds for drug-likeness, 44 were docked against c-Abl kinase. The top hit compound (isovitexin) and nilotinib (control drug) were subjected to rigorous analyses, including ADMET profiling, DFT evaluation, and MDS for 100 ns. Isovitexin demonstrated a notable binding affinity (-15.492 kcal/mol), closely comparable to nilotinib (-16.826 kcal/mol), showcasing a similar binding pose and superior structural stability and reactivity. While these findings suggest isovitexin as a potential c-Abl kinase inhibitor, further validation through urgent in vitro and in vivo experiments is imperative. This research holds promise for providing an alternative avenue to address existing CML treatment and management challenges.Communicated by Ramaswamy H. Sarma.

3.
Int Nurs Rev ; 2024 Mar 04.
Article En | MEDLINE | ID: mdl-38436471

AIMS: The aim was to investigate the interrelationships of nurses' safety climate, quality of care, and adherence to and compliance with standard precautions (SPs). BACKGROUND: Investigations about nurses' safety climate and quality care and their association with adherence to and compliance with SPs remain remarkably scant across literature, specifically among developing countries like the Philippines. DESIGN: Cross-sectional design and structural equation modeling (SEM) approach while complying with STROBE guidelines. METHODS: Participant nurses were recruited using convenience sampling (n = 870). Four validated self-report instruments were used to collect data from February to August 2022. Spearman rho, SEM, mediation, and path analyses were employed for data analysis. RESULTS: The emerging model showed acceptable model fit parameters. The safety climate positively influenced the quality of care and adherence to and compliance with SPs. Quality of care directly affected adherence to SPs, while adherence to SPs directly affected compliance with SPs. The quality of care mediated the relationship between safety climate and adherence to SPs. Whereas adherence to SPs mediated the relationships between safety climate and compliance with SPs and the quality of care and compliance with SPs. CONCLUSIONS: Nurses' safety climate directly affected the quality of care and SPs adherence and compliance. The quality of care mediated the impact of safety climate on SPs adherence. Finally, SPs adherence demonstrated a mediating effect among quality of care, safety climate, and SPs compliance. IMPLICATIONS FOR NURSING POLICY AND PRACTICE: Nursing policymakers and administrators can use the findings to design strategic policies and sustainable in-service educational courses fostering and maintaining nurses' safety climate, quality of care, and SPs adherence and compliance.

4.
Pharmacy (Basel) ; 12(2)2024 Feb 27.
Article En | MEDLINE | ID: mdl-38525722

Background: The global burden of colorectal cancer remains a major public health issue and one of the leading causes of death worldwide. In Saudi Arabia, it continues to be a health concern. Any delays in diagnosis for any reason may contribute to advanced complications; therefore, pharmacists' knowledge and awareness of colorectal cancer are crucial for the welfare of society. Studies of colon cancer-related knowledge, attitude, and practice (KAP) among community pharmacists have not previously been conducted in the Al-Qassim region of Saudi Arabia. In the present study, therefore, we sought to investigate the KAP on colon cancer among pharmacists in Al-Qassim. Methods: This was a prospective, cross-sectional, observational study. A sample of 150 community pharmacists was recruited using a convenience sampling method. A self-administered questionnaire was used to evaluate levels of knowledge and practice. Results: Out of a total of 150 pharmacists, the majority of respondents (60.7%) possessed an adequate level of knowledge. About 50% of participants had heard of the early screening test, and 68.7% knew that colonoscopy is necessary in such scenarios. On the basis of their attitudes, 41.3% of study participants were aware of colon cancer symptoms and risk factors. In practice, however, the majority of pharmacists (81%) did not perform early cancer screenings, while 19% did screen when advised to do so by a physician. Conclusions: Our results indicate that pharmacists in Qassim have an adequate level of knowledge of colon cancer in terms of awareness, assessment, and screening. Since community pharmacists are among the most reliable members of the medical community, a greater awareness of colon cancer among pharmacists may improve public knowledge of the disease.

5.
JMIR Form Res ; 8: e54500, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38488833

BACKGROUND: Electronic learning refers to the use of assistive tools in offline and distance learning environments. It allows students to access learning tools and materials anytime and anywhere. However, distance learning courses depend on several factors that affect the quality of learning, which consequently affect students' preferences in the settings and tools used to deliver educational materials. OBJECTIVE: This study aimed to evaluate students' preferences for continuing distance learning after the pandemic and to assess the distance educational environment after the pandemic. It also aimed to identify the factors affecting distance learning and evaluate students' preferences regarding modes of communication with instructors. METHODS: A web-based survey was used to conduct this cross-sectional study. The target participants of this study were students in the doctor of pharmacy program at Unaizah College of Pharmacy, Qassim, Saudi Arabia. All students enrolled from December 2022 to January 2023 received an invitation with a link to the web-based survey. RESULTS: The survey was completed by 141 students (58 female students and 83 male students). The research results showed that most students (102/141, 72.3%) did not wish to continue distance education for laboratory courses, and 60.3% (85/141) did not wish to continue taking distance team-based learning after the pandemic. Additionally, 83.7% (118/141) of the students indicated that distance courses were simple. More than half of the participants (79/141, 56%) stated that having a camera on during class negatively impacted their learning, and only 29.1% (41/141) of the students stated that nonvisual communication with their fellow students impacted their learning. A large proportion of students (83/141, 58.9%) reported impairment of social engagement on campus, 44% (62/141) in-person interactions during classes, and 73.7% (104/141) were relieved that their classes were not disrupted. CONCLUSIONS: Similar to all types of education, distance learning is characterized by advantages and disadvantages, as reported by students. Students felt that the course material was intelligible, and the distance course was uncomplicated. Moreover, they expressed relief that their studies were not disrupted. However, they also reported the loss of face-to-face contact during courses as the most significant drawback of distance learning versus face-to-face learning, followed by a lack of social connection on campus.

6.
PLoS One ; 19(2): e0294286, 2024.
Article En | MEDLINE | ID: mdl-38386950

This study highlights the effectiveness of oyster shell biocomposite for the biosorption of Cd(II) and Pb(II) ions from an aqueous solution. The aim of this work was to modify a novel biocomposite derived from oyster shell for the adsorption of Cd(II) and Pb(II) ions from aqueous solution. The studied revealed the specific surface BET surface area was 9.1476 m2/g. The elemental dispersive x-ray analysis (EDS) indicated that C, O, Ag, Ca were the predominant elements on the surface of the biocomposite after which metals ions of Cd and Pb were noticed after adsorption. The Fourier transform Irradiation (FT-IR) revealed the presence of carboxyl and hydroxyl groups on the surface. The effect of process variables on the adsorption capacity of the modified biocomposite was examined using the central composite design (CCD) of the response surface methodology (RSM). The process variables which include pH, adsorbent dose, the initial concentration and temperature were the most effective parameters influencing the uptake capacity. The optimal process conditions of these parameters were found to be pH, 5.57, adsorbent dose, 2.53 g/L, initial concentration, 46.76 mg/L and temperature 28.48°C for the biosorption of Cd(II) and Pb(II) ions from aqueous solution at a desirability coefficient of 1. The analysis of variance (ANOVA) revealed a high coefficient of determination (R2 > 0.91) and low probability coefficients for the responses (P < 0.05) which indicated the validity and aptness of the model for the biosorption of the metal ions. Experimental isotherm data fitted better to the Langmuir model and the kinetic data fitted better to the pseudo-second-order model. Maximun Cd(II) and Pb(II) adsorption capacities of the oyster shell biocomposite were 97.54 and 78.99 mg/g respectively and was obtained at pH 5.56 and 28.48°C. This investigation has provided the possibility of the utilization of alternative biocomposite as a sustainable approach for the biosorption of heavy metal ions from the wastewater stream.


Cadmium , Ostreidae , Animals , Cadmium/analysis , Spectroscopy, Fourier Transform Infrared , Adsorption , Lead , Ions
7.
J Biomol Struct Dyn ; : 1-14, 2024 Jan 04.
Article En | MEDLINE | ID: mdl-38213287

The trypanothione reductase enzyme, which neutralizes the reactive oxygen species produced inside the macrophages to kill the parasites, is one of the evasion strategies Leishmania uses to survive inside the cells. The vitality of the parasite depends on Leishmania major trypanothione reductase (LmTr), a NADPH-dependent flavoprotein oxidoreductase essential for thiol metabolism. Since this enzyme is distinct and lacking in humans, we focused on it in our study to screen for new inhibitors to combat leishmaniasis. Using the I-TASSER server, a three-dimensional model of LmTr was generated. The Autodock vina program was used in high-throughput virtual screening of the ZINC database. The top seven molecules were ranked according to their binding affinity. The compounds with the highest binding affinities and the right number of hydrogen bonds were chosen. These compounds may be effective at inhibiting the target enzyme's (LmTr) activity, making them new leishmaniasis treatments. These compounds may serve as a useful starting point for a hit-to-lead approach in the quest for new anti-Leishmania drugs that are more efficient and less cytotoxic. The average node degree is 5.09, the average local clustering coefficient is 0.868, and the PPI enrichment p-value is 8.9e-06, indicating that it is sufficiently connected to regulate the network. TRYR (LmTr protein) also interacts physically with ten additional proteins in the pathogenesis network. The findings of the study indicated that successfully suppressing the LmTr protein in vitro and in vivo may finally result in regulating the L. major pathogenesis.Communicated by Ramaswamy H. Sarma.

8.
J Biomol Struct Dyn ; 42(3): 1307-1318, 2024.
Article En | MEDLINE | ID: mdl-37139557

Ubiquitin specific protease 30 (USP30) has been attributed to mitochondrial dysfunction and impediment of mitophagy in Parkinson's disease (PD). This happens once ubiquitin that supposed to bind with deformed mitochondria at the insistence of Parkin, it's been recruited by USP30 via the distal ubiquitin binding domain. This is a challenge when PINK1 and Parkin loss their functions due to mutation. Although, there are reports on USP30s' inhibitors but no study on the repurposing of inhibitors approved against MMP-9 and SGLT-2 as potential inhibitors of USP30 in PD. Thus, the highlight therein, is to repurpose approved inhibitors of MMP-9 and SGLT-2 against USP30 in PD using extensive computational modelling framework. 3D structures of Ligands and USP30 were obtained from PubChem and protein database (PDB) servers respectively, and were subjected to molecular docking, ADMET evaluation, DFT calculation, molecular dynamics simulation (MDS) and free energy calculations. Out of the 18 drugs, 2 drugs showed good binding affinity to the distal ubiquitin binding domain, moderate pharmacokinetic properties and good stability. The findings showed canagliflozin and empagliflozin as potential inhibitors of USP30. Thus, we present these drugs as repurposing candidates for the treatment of PD. However, the findings in this current study needs to be validated experimentally.Communicated by Ramaswamy H. Sarma.


Parkinson Disease , Humans , Parkinson Disease/genetics , Matrix Metalloproteinase 9 , Molecular Docking Simulation , Drug Repositioning , Protein Kinases/metabolism , Mitochondrial Proteins/chemistry , Thiolester Hydrolases/chemistry , Thiolester Hydrolases/genetics , Thiolester Hydrolases/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin/metabolism , Ubiquitin-Specific Proteases/metabolism
9.
Medicina (Kaunas) ; 59(12)2023 Nov 21.
Article En | MEDLINE | ID: mdl-38138153

Background and Objectives: In 2020, one of the most important steps that were made was to give priority to the development of a COVID-19 vaccine to prevent the rising incidence of COVID-19 from continuing to rise. However, globally, there is a variable acceptance of the level of the COVID-19 vaccine. This study aims to explore Saudi parents' willingness to vaccinate their children against COVID-19. Materials and Methods: This was a cross-sectional study; the online questionnaire was used to investigate the views of Saudi parents with children aged under 18 toward the immunization of their children against COVID-19. The data were gathered from 10 May 2022 to 31 October 2022. The data analysis uses SPSS version 20. A p-value of 0.05 or lower was regarded as statistically significant. Results: A total of 978 Saudi parents participated in this study. Most of the respondents were from the age group of 36-45 years with the educational qualification of high school and bachelor's degree. Overall, it was observed that the majority, 98.2% of the respondents, disclosed that they needed more information (p = 0.004) about COVID-19 vaccine safety among children so that they could decide whether to vaccinate their child. About 91.4% of parents mention that vaccination against COVID-19 is not necessary for children (p = 0.001). About 68.3% of respondents agreed that getting vaccinated against COVID-19 could help Saudi Arabia control COVID-19 (p = 0.007, RI = 0.76). In terms of negative attitudes toward COVID-19 vaccination, 71.3% think that there will be severe side effects (p = 0.019, RI = 0.75); 67.7% think that the vaccine's protection will only last for a short time (p = 0.055, RI = 0.72); 80.1% said they were afraid of getting vaccinated because of needle fear (p = 0.045, RI = 0.76), and 41.2% said lack of time was the main barrier to not vaccinating their child. Conclusions: Parents expressed concerns regarding the safety and efficacy of the COVID-19 vaccine, which might be some of the main factors influencing their decision to vaccinate their children. It is the need of the hour to take action to communicate, educate, and intervene with Saudi parents to enhance COVID-19 vaccination compliance rates across the board.


COVID-19 Vaccines , COVID-19 , Child , Humans , Adult , Middle Aged , COVID-19 Vaccines/therapeutic use , Cross-Sectional Studies , COVID-19/epidemiology , COVID-19/prevention & control , Saudi Arabia/epidemiology , Vaccination
10.
RSC Adv ; 13(46): 32786-32823, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-37942448

Spiro-heterocycles have received special attention in medicinal chemistry because of their promising biological activity. Over the years, many synthetic methodologies have been established for the construction of spirocyclic compounds. Spiro heterocycles such as spiro-azetidin-2-one, -pyrrolidine, -indol(one) and -pyran derivatives have been found to exhibit diversified biological and pharmacological activity in addition to their therapeutic properties. In view of these facts, we decided in this review to present representative synthetic approaches of the aforementioned spiro heterocycles, especially in the past 20 years.

11.
Pharmacy (Basel) ; 11(5)2023 Sep 21.
Article En | MEDLINE | ID: mdl-37736924

BACKGROUND: Electronic prescribing systems (e-prescription) for medications have many benefits, including patient safety, increase in patient satisfaction, efficiency of pharmacy work, and quality of patient care. However, few studies have been conducted to evaluate the national e-prescription system "Wasfaty" service in Saudi Arabia, which was recently adopted. OBJECTIVE: The aims of this study were to explore the benefits observed through the use of the system and most frequent challenges experienced by community pharmacists in the Qassim region of Saudi Arabia. METHODS: This study was conducted using a descriptive survey on a web-based platform. The target population of the study included community pharmacists in the Qassim region of Saudi Arabia who worked in pharmacy chains utilizing the e-prescription service between September 2022 and November 2022. Descriptive statistics along with multiple ordinal regression were used for data analysis. RESULTS: The study population consisted of 124 pharmacists, of which 62.9% (78/124) were males and 37.1% (46/124) were females. Most of the participants had a positive perception of the e-prescription system with regard to medication safety, with 68.6% (85/124) indicating that e-prescriptions reduce the risk of dispensing errors. However, 81.5% (101/124) did not agree that the e-prescription system resulted in a reduction in workload, and 70.2% (87/124) disagreed that the service increased patient satisfaction. CONCLUSIONS: The results of this study indicated that the national e-prescription system has many benefits to healthcare employees and improves their work, particularly for patient safety, reducing medication errors, and improving the management of patient medications. The participants believe that there is a need to improve communication with prescribers, showing concern about the unavailability of some medications; thus, it is important for policymakers to encourage other pharmacy chains and suppliers to join the service to increase patient access to medications.

12.
BMC Nurs ; 22(1): 308, 2023 Sep 07.
Article En | MEDLINE | ID: mdl-37674203

BACKGROUND: The nursing profession has significant importance in delivering high-quality healthcare services. Nursing practitioners who have essential competencies and who are satisfied with their job are vital in achieving optimum patient outcomes. Understanding the effects of technology integration on nurse workforce competencies and job satisfaction is crucial due to the fast progress of technology in healthcare settings. Furthermore, many elements, including self-efficacy, social support, and prior experience have been recognized as possible mediators or moderators within this association. The primary objective of this quantitative research was to examine the influence of nursing education and the integration of technology on the competencies and job satisfaction of nursing professionals. Additionally, this study aimed to explore the potential mediating and moderating effects of self-efficacy and social support in this relationship. METHODS: This cross-sectional, quantitative study employed an online survey questionnaire with standardized scales to measure nursing workforce competencies, job satisfaction, self-efficacy, social support, and prior experience. It was completed by 210 registered nurses from various healthcare settings in the Kingdom of Saudi Arabia. Data were analyzed by descriptive statistics, Pearson correlation analysis, multiple regression analysis, and structural equation modeling performed with SPSS 23 and SmartPLS 3.0 software. RESULTS: The study's findings revealed that nursing workforce competencies and job satisfaction were significantly predicted by nursing training and technology integration. The relationship between nursing training and technology integration, as well as nursing workforce competencies and job satisfaction, was partially mediated by self-efficacy and social support. Furthermore, prior experience moderated the relationship between nursing education and technological integration, nursing workforce competencies, and job satisfaction. CONCLUSIONS: The study's findings suggest that nursing training and technology integration can improve nursing workforce competencies and job satisfaction and that self-efficacy and social support play an important role in mediating this relationship. Furthermore, prior experience can have an impact on the efficacy of nursing training and technology integration programs for developing nursing workforce competencies. The study has several practical implications for nursing education, training, and professional development programs, as well as strategies used by healthcare organizations to improve nursing workforce competencies and job satisfaction. To maximize their impact on nursing workforce competencies and job satisfaction, this study recommends that nursing training and technology integration programs focus on enhancing self-efficacy and social support. Furthermore, the study emphasizes the significance of prior experience when designing and implementing nursing training and technology integration programs.

13.
Front Pediatr ; 11: 1206389, 2023.
Article En | MEDLINE | ID: mdl-37681202

Background: Neonatal early onset sepsis (NEOS) is a serious and potentially life-threatening condition affecting newborns within the first few days of life. While the diagnosis of NEOS was based on clinical signs and symptoms in the past, recent years have seen growing interest in identifying specific diagnostic factors and optimizing therapy outcomes. This study aims to investigate the diagnostic and risk factors and therapy outcomes of neonatal EOS in ICU patients in Saudi Arabia, with the goal of improving the management of neonatal EOS in the country. Methods: This method outlines the protocol development, search strategy, study selection, and data collection process for a systematic review on neonatal early onset sepsis in Saudi Arabian ICU patients, following the PRISMA 2020 guidelines. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) is a well-established guideline that provides a framework for conducting systematic reviews and meta-analyses in a transparent and standardized manner. It aims to improve the quality and reporting of such research by ensuring clear and comprehensive reporting of study methods, results, and interpretations. The search strategy included electronic databases (PubMed, Embase, Google Scholar, Science Direct, and the Cochrane Library) and manual search of relevant studies, and data were extracted using a standardized form. Results: The systematic review included 21 studies on neonatal sepsis in Saudi Arabia, with varying study designs, sample sizes, and prevalence rates of sepsis. Group B streptococcus and E. coli were the most commonly isolated pathogens. Various diagnostic factors and risk factors were reported, including hematological parameters, biomarkers, and blood cultures. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute critical checklist. Conclusions: The review identified a number of risk and diagnostic factors and therapy outcomes for neonatal sepsis. However, most of the studies were having small scale cohort groups. Further research with controlled study designs is needed to develop effective prevention and management strategies for neonatal sepsis in Saudi Arabia.

14.
Article En | MEDLINE | ID: mdl-37659050

Pain management has been a severe public health issue throughout the world. Acute pain if not treated at the appropriate time can lead to chronic pain that can cause psychological and social distress. Nothing can be more rewarding than treating pain successfully for a physician. However, the use of chemical NSAIDs and opiate drugs has taken a toll on the patients with their unavoidable side effects. This study intends to explore the potential to treat pain by inhibiting nociception and inflammation with a safer, non-addictive, effective, and low-cost alternative agent from a natural source, visnagin. In vivo studies have been conducted using male Swiss albino mice as models for this research. Nociception was induced using different chemical and thermal stimuli such as acetic acid, glutamate, capsaicin, and formalin. To check for the anti-inflammatory properties, carrageenan was used to induce inflammation and the activity was assayed using peritoneal cavity leukocyte infiltration analysis and pro-inflammatory cytokine level comparison with the supplementation of visnagin at three different dosages. The findings of this study revealed that the visnagin treatment effectively attenuated the acetic acid-induced writhing response, glutamate-induced paw licking numbers, capsaicin-induced pain response, and formalin-induced biphasic licking incidences in the experimental mice models. Furthermore, the visnagin treatment remarkably suppressed the carrageenan-induced inflammation in mice, which is evident from the decreased leukocytes, mononuclear, and polymorphonuclear cell numbers in the mice. The levels of cytokines such as TNF-α, IL-1ß, and IL-6 were effectively reduced by the visnagin treatment in the experimental mice. The results of open field test proved that the visnagin showed a better locomotor movement in the experimental mice. These results provided evidence for the potential activity of the visnagin against inflammatory and nociceptive responses in the mice.

15.
Cancers (Basel) ; 15(18)2023 Sep 10.
Article En | MEDLINE | ID: mdl-37760469

The genesis of cancer is a precisely organized process in which normal cells undergo genetic alterations that cause the cells to multiply abnormally, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Potential drugs that could modify these carcinogenic pathways are the ones that will be used in clinical trials as anti-cancer drugs. Resveratrol (RES) is a polyphenolic natural antitoxin that has been utilized for the treatment of several diseases, owing to its ability to scavenge free radicals, control the expression and activity of antioxidant enzymes, and have effects on inflammation, cancer, aging, diabetes, and cardioprotection. Although RES has a variety of pharmacological uses and shows promising applications in natural medicine, its unpredictable pharmacokinetics compromise its therapeutic efficacy and prevent its use in clinical settings. RES has been encapsulated into various nanocarriers, such as liposomes, polymeric nanoparticles, lipidic nanocarriers, and inorganic nanoparticles, to address these issues. These nanocarriers can modulate drug release, increase bioavailability, and reach therapeutically relevant plasma concentrations. Studies on resveratrol-rich nano-formulations in various cancer types are compiled in the current article. Studies relating to enhanced drug stability, increased therapeutic potential in terms of pharmacokinetics and pharmacodynamics, and reduced toxicity to cells and tissues are the main topics of this research. To keep the readers informed about the current state of resveratrol nano-formulations from an industrial perspective, some recent and significant patent literature has also been provided. Here, the prospects for nano-formulations are briefly discussed, along with machine learning and pharmacometrics methods for resolving resveratrol's pharmacokinetic concerns.

16.
Antibiotics (Basel) ; 12(8)2023 Aug 21.
Article En | MEDLINE | ID: mdl-37627763

Suboptimal antibiotics use and the development of antibiotic resistance is a universal calamity. The theoretical model of therapeutic efficacy correlates quality use of antibiotics with healthcare practitioners' understanding of antibiotic use and resistance. Keeping this phenomenon in mind, we aimed to evaluate hospital pharmacists' understanding of antibiotic use and resistance at a public healthcare institute in Quetta city, Pakistan. This was a qualitative study that employed a semi-structured interview guide for data extraction. The phenomenology-based approach commissioned in-depth, face-to-face interviews with hospital pharmacists stationed at the surgical unit of Sandeman Provincial Hospital, Quetta. The interviews were audio taped followed by transcribed verbatim and were then analyzed for thematic contents by the standard content analysis framework. Although the saturation was reached after the 10th interview, we conducted two additional interviews for definite validation. Content analysis revealed five major themes: (1) Defining antibiotics, quality use of antibiotics and resistance, (2) antibiotic use: awareness and concern, (3) antimicrobial resistance: awareness and concern, (4) responding to antibiotic use and resistance, and (5) barriers to quality use of antibiotics and prevention of antibiotic resistance. The knowledge of quality use of antibiotics and resistance was promising, and the respondents were eager to address the drastic situation. The respondents were aware of the critical situation and provided valuable insights that can offer valued input while promoting the quality use of antibiotics in a developing country. The current study managed to identify an adequate understanding of antibiotic use and resistance among hospital pharmacists. Additionally, prospective concerns and possible predictors of antibiotic resistance were also highlighted. The current findings must be disseminated to the policymakers and prescribers to take prompt restorative actions to address antibiotic use and the development of antibiotic resistance in a developing country like Pakistan.

17.
J Biochem Mol Toxicol ; 37(10): e23433, 2023 Oct.
Article En | MEDLINE | ID: mdl-37394811

In this work, four fluorinated α, ß-unsaturated ketones named as 3-(3-bromophenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (1), 3-(4-methoxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (2), 3-(3-bromo-5-chloro-2-hydroxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (3) and 3-(2-hydroxy-5-methylphenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4) were synthesized by Claisen-Schmidt reaction. The synthesized molecules were then characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), 1 H-NMR, 13 C-NMR, and mass spectrometry. The antioxidant potential, Urease inhibition, and interaction of compounds 1-4 with Salmon sperm DNA were experimentally explored and supported by molecular docking studies. The synthesized compounds strongly interact with SS-DNA through intercalative mode. It was noticed that compound 1 served as potent Urease inhibitor while compound 4 as better antioxidant among synthesized compounds. Moreover, frontier molecular orbitals, nonlinear optical (NLO) properties, natural bond orbitals, molecular electrostatic potential, natural population analysis, and photophysical properties of synthesized compounds were accomplished through density functional theory and time-dependent density functional theory. The band gap of all the compounds have been worked out using Taucs method. In addition to that, a precise comparative account of UV and IR data obtained from theoretical and experimental findings showed good agreement between theoretical and experimental data. The findings of our studies reflected that compounds 1-4 possess better NLO properties than Urea standard and the band gap data also reflected their prospective use towards optoelectronic materials. The better NLO behavior of compounds was attributed to the noncentrosymmetric structure of synthesized compounds.


Antioxidants , Urease , Male , Humans , Models, Molecular , Molecular Docking Simulation , Spectroscopy, Fourier Transform Infrared , Semen , DNA , Spectrophotometry, Ultraviolet
18.
Medicina (Kaunas) ; 59(7)2023 07 02.
Article En | MEDLINE | ID: mdl-37512049

Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient's medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization's Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.


Antimicrobial Stewardship , Vancomycin , Humans , Linezolid/pharmacology , Linezolid/therapeutic use , Pakistan , Anti-Bacterial Agents/therapeutic use , Piperacillin, Tazobactam Drug Combination , Hospitals
19.
Medicina (Kaunas) ; 59(7)2023 Jul 09.
Article En | MEDLINE | ID: mdl-37512090

Background and Objectives: Group B streptococcus (GBS) is the leading cause of infections in neonates with high fatality rates. GBS is caused by the streptococcus bacterium known as streptococcus agalactiae, which is highly contagious and can be transmitted from pregnant women to infants. GBS infection can occur as an early onset or late-onset infection and has different treatment strategies. Antibiotics are effective in treating GBS infections at early stages. The aim of this systematic review was to summarize the clinical characteristics and treatment strategies for GBS, with a focus on antibiotics. Material and Methods: The findings of this review were reported in accordance with the PRISMA 2020 guidelines and a flow diagram of the study selection process, a summary of the included studies, a description of the study characteristics, a summary of the results, a discussion of the implications of the findings, and a conclusion are included. Overall, the authors followed a rigorous methodology to ensure that this review is comprehensive and inclusive of relevant studies on GBS infection and its treatment. Results: Overall, 940 studies were reviewed and only the most relevant 22 studies were included in the systematic review. This review describes the characteristics of patients in different studies related to early onset GBS disease and presents various treatment strategies and outcomes for GBS infection in pediatrics. The studies suggest that preventive measures, risk-based intrapartum antibiotic prophylaxis, and maternal vaccination can significantly reduce the burden of GBS disease, but late-onset GBS disease remains a concern, and more strategies are required to decrease its rate. Improvement is needed in the management of the risk factors of GBS. A conjugate vaccine with a serotype (Ia, Ib, II, III, and V) has been proven effective in the prevention of GBS in neonates. Moreover, penicillin is an important core antibiotic for treating early onset GBS (EOD). Conclusions: This systematic review summarizes the treatment comparison for GBS infections in neonates, with a primary focus on antibiotics. IAP (intrapartum antibiotic prophylaxis) according to guidelines, antenatal screening, and the development of a conjugate vaccine may be effective and could lower the incidence of the disease.


Pediatrics , Streptococcal Infections , Infant , Infant, Newborn , Humans , Female , Pregnancy , Child , Streptococcus agalactiae , Vaccines, Conjugate/therapeutic use , Infectious Disease Transmission, Vertical/prevention & control , Anti-Bacterial Agents/therapeutic use , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapy , Streptococcal Infections/prevention & control
20.
J Pharm Policy Pract ; 16(1): 89, 2023 Jul 14.
Article En | MEDLINE | ID: mdl-37452388

INTRODUCTION: Despite the paucity of scientific evidence, CAM is widely used for the prevention and treatment of illness among patients with chronic kidney disease, including end-stage renal disease and kidney transplant recipients. It is evident that the irrational use of CAM among CKD patients and its non-disclosure to healthcare providers could lead to adverse drug events. Hence, the current study was conducted to evaluate the prevalence, types, and non-disclosure of CAM use among CKD patients and kidney transplant recipients in Saudi Arabia. METHODS: A cross-sectional study was conducted on 170 CKD patients (121 with stages 3 and 4, two with stage 5 and on hemodialysis, and 47 kidney transplant recipients). Face-to-face questionnaire-based interviews were conducted employing a convenience sampling technique. The study outcomes were the prevalence of CAM, types of CAM use, monthly expenditure on CAM, the source of information about CAM, and CAM disclosure to healthcare providers. A p-value of < 0.05 was considered significant. RESULTS: The study found that out of 170, 60 (35.3%) CKD patients use CAM. The most used CAM was Acacia gum (49, 81.6%) followed by spiritual therapies (34, 56.6%). Female CKD patients had higher use of CAM compared to the male gender (p = 0.015). The monthly expenditures that most users (47, 78.3%) spent on CAM were less than 50 Saudi Riyals (SR). The study results also showed that 55% of CKD patients did not report their CAM use to their physicians. Furthermore, 46.6% of CAM users discontinue their use of CAM after observing no benefit. CONCLUSION: This study reported relatively high use of CAM among CKD patients in Saudi Arabia. The study found that most CKD patients use Acacia gum and spiritual therapies and do not disclose the use of CAM to healthcare professionals, which could lead to adverse drug events. Therefore, the study recommends that healthcare providers should inquire and provide evidence-based counselling about the use of CAM to CKD patients to prevent any adverse drug event or unwanted effect on the renal function of the patients.

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