Munjal K, Goel Y, Gauttam VK
… +5 more, Chopra H, Singla M, Smriti, Gupta S, Sharma R
Drug Target Insights
· 2024 · PMID 38873988
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AIM: Researchers using herbs and natural products to find new drugs often prefer flavonoids because of their potential as antioxidants and anti-inflammatories. The planned review addressed baicalein research findings in...AIM: Researchers using herbs and natural products to find new drugs often prefer flavonoids because of their potential as antioxidants and anti-inflammatories. The planned review addressed baicalein research findings in detail. This manuscript provides a complete review of baicalein's potential pharmacological effects along with several molecular targets for better understanding of its therapeutic activities. MATERIALS AND METHODS: We targeted the review on in vitro and in vivo studies reported on baicalein. For this, the literature is gathered from the database available on search engines like PubMed, ScienceDirect, Scopus, and Google Scholar up to 21 December 2023. The keywords "", "", "", "", "", and "" were used to fetch the content. RESULTS: Baicalein's molecular receptor binding approach has shown anticancer, antidiabetic, antimicrobial, antiaging, neuroprotective, cardioprotective, respiratory protective, gastroprotective, hepatic protective, and renal protective effects. The synergistic effects of this drug with other selective herbs are also contributed towards significant therapeutic potential. CONCLUSION: This systematic review article from a contemporary and scientific perspective offers fresh insight into , , and its bioactive component baicalein as a potential complementary medicine. Baicalein may be transformed into more efficacious and acceptable evidence-based medicine. However, we recommend more clinical and mechanistic approaches to confirm safety and efficacy of baicalein.
Gupta DL, Meher J, Giri AK
… +4 more, Shukla AK, Mohapatra E, Ruikar MM, Rao DN
Drug Target Insights
· 2024 · PMID 38860262
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INTRODUCTION: It is unclear whether induced spike protein-specific antibodies due to infections with SARS-CoV-2 or to the prototypic Wuhan isolate-based vaccination can immune-react with the emerging variants of SARS-CoV...INTRODUCTION: It is unclear whether induced spike protein-specific antibodies due to infections with SARS-CoV-2 or to the prototypic Wuhan isolate-based vaccination can immune-react with the emerging variants of SARS-CoV-2. AIM/OBJECTIVES: The main objective of the study was to measure the immunoreactivity of induced antibodies postvaccination with Covishield™ (ChAdOx1 nCoV-19 coronavirus vaccines) or infections with SARS-CoV-2 by using selected peptides of the spike protein of wild type and variants of SARS-CoV-2. METHODOLOGY: Thirty patients who had recovered from SARS-CoV-2 infections and 30 individuals vaccinated with both doses of Covishield™ were recruited for the study. Venous blood samples (5 mL) were collected at a single time point from patients within 3-4 weeks of recovery from SARS-CoV-2 infections or receiving both doses of Covishield™ vaccines. The serum levels of total immunoglobulin were measured in both study groups. A total of 12 peptides of 10 to 24 amino acids length spanning to the receptor-binding domain (RBD) of wild type of SARS-CoV-2 and their variants were synthesized. The serum levels of immune-reactive antibodies were measured using these peptides. RESULTS: The serum levels of total antibodies were found to be significantly (p<0.001) higher in the vaccinated individuals as compared to COVID-19 recovered patients. Our study reported that the mutations in the RBD at the residues K417, E484, and N501 have been associated with reduced immunoreactivity with anti-sera of vaccinated people and COVID-19 recovered patients. CONCLUSION: The amino acid substitutions at the RBD of SARS-CoV-2 have been associated with a higher potential to escape the humoral immune response.
Natsheh IY, Alsaleh MM, Alkhawaldeh AK
… +3 more, Albadawi DK, Darwish MM, Shammout MJA
Drug Target Insights
· 2024 · PMID 38751378
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Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing thi...Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields-cardiovascular, cancer, and diabetes-and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.
Babyshkina N, Popova N, Grigoryev E
… +7 more, Dronova T, Gervas P, Dobrodeev A, Kostromitskiy D, Goldberg V, Afanasiev S, Cherdyntseva N
Drug Target Insights
· 2024 · PMID 38283860
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Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction betw...Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients. However, its efficacy is extremely limited in microsatellite stability (MSS)/mismatch repair proficient (pMMR) patients. We report a case of a 42-year-old man diagnosed with MSS/pMMR mCRC who has achieved a durable response to nivolumab after a progression under chemotherapy with antiangiogenic treatment. We observed for the first time an atypical response after 8 months of nivolumab treatment, with the regression of previous primary pulmonary lesions and the presence of new para-aortic lymph node lesions. This report demonstrates that a subset of pretreated mCRC patients with the MSS/pMMR phenotype may benefit from nivolumab and these patients need more attention.
Diarra L, Mariko M, Traore S
… +8 more, Dicko SB, Dolo A, Coulibaly M, Sidibé D, Daou M, Poma H, Traore M, Guindo I
Drug Target Insights
· 2024 · PMID 38239935
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BACKGROUND: Non-compliance in the drafting of examination bulletins makes it difficult to perform them and interpret the results. With the aim of continuously improving laboratory services and guaranteeing the quality of...BACKGROUND: Non-compliance in the drafting of examination bulletins makes it difficult to perform them and interpret the results. With the aim of continuously improving laboratory services and guaranteeing the quality of urine cytobacteriological examination (ECBU) results, we initiated this study to evaluate non-compliance in the drafting of ECBU reports. MATERIALS AND METHODS: This was a retrospective descriptive cross-sectional study which focused on non-compliance in the drafting of ECBU reports analysed in the laboratory from January to December 2022. RESULTS: During the study period, we collected 383 non-compliant ECBU reports out of 672, with a frequency of 56.99%. Non-compliances were related to age (2.68%), profession (24.40%), clinical information (6.70%) and residence (52.08%). The majority of non-compliant reports came from the medicine (35.51%) and urology (25.85%) departments. CONCLUSION: The high frequency of non-compliance is a cause for concern and is of concern to all prescribers in this hospital.
Drug Target Insights
· 2023 · PMID 38124759
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Urinary tract infections (UTIs) are among the most common infections globally, imposing a substantial personal and economic burden on individuals and health resources. Despite international health concerns and sustained...Urinary tract infections (UTIs) are among the most common infections globally, imposing a substantial personal and economic burden on individuals and health resources. Despite international health concerns and sustained public awareness campaigns about the emergence of resistant microorganisms through the inappropriate therapeutic use of antimicrobial agents, the problem of antimicrobial resistance (AMR) is worsening, and AMR in UTIs represents a critical global healthcare issue. This narrative review summarizes evidence-based scientific material, recommendations from the current medical literature, and the latest clinical guidelines on antibiotic and antibiotic-sparing strategies for managing urological infections, including practical approaches to improve the management of patients with acute and recurrent UTIs (rUTIs) in routine clinical practice. Novel emerging therapies and prophylaxis options are described as potential alternatives to overcome the abuse and overuse of antibiotics and the practical application of the guideline recommendations and issues relating to best practice in managing UTIs.
So-Ngern A, Osaithai N, Meesing A
… +1 more, Chumpangern W
Drug Target Insights
· 2023 · PMID 38028024
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BACKGROUND:: Carbapenem-resistant Enterobacteriaceae (CRE) is a serious pathogen with high mortality. Recognition of factors associated with mortality and treating these modifiable factors are crucial to reducing mortali...BACKGROUND:: Carbapenem-resistant Enterobacteriaceae (CRE) is a serious pathogen with high mortality. Recognition of factors associated with mortality and treating these modifiable factors are crucial to reducing mortality. OBJECTIVE:: To determine the 30-day mortality and factors associated with a 30-day mortality of CRE infection. METHODS:: A retrospective cohort study was conducted between January 1, 2015, and December 31, 2019. All patients diagnosed with CRE infection aged ≥18 years were included. Multivariate logistic regression was used for evaluating the factors associated with 30-day mortality and presented as adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULT:: One hundred and ninety-four patients were enrolled. The 30-day mortality occurred in 75 patients (38.7%). The common antibiotic regimen was monotherapy and combination of carbapenem, colistin, amikacin, tigecycline, and fosfomycin. CRE isolates were susceptible to tigecycline (93.8%), colistin (91.8%), fosfomycin (89.2%), and amikacin (89.2%). The independent factors associated with 30-day mortality were an increasing simplified acute physiology (SAP) II score (aOR 1.11, 95% CI 1.05-1.16, p < 0.001), sepsis at time of CRE infection diagnosis (aOR 7.93, 95% CI 2.21-28.51, p = 0.002), pneumonia (aOR 4.48, 95% CI 1.61-12.44, p = 0.004), monotherapy (aOR 4.69, 95% CI 1.71-12.85, p = 0.003), and improper empiric antibiotic (aOR 5.13, 95% CI 1.83-14.40, p = 0.002). CONCLUSION:: The overall 30-day mortality of CRE infection was high. The factors associated with mortality were an increasing SAP II score, sepsis at time of CRE infection diagnosis, pneumonia, monotherapy, and improper empiric antibiotic. The study suggested that proper empiric antibiotic and combination antibiotics might reduce mortality from CRE infection.
Inno A, Bogina G, Settanni G
… +5 more, Salgarello M, Foti G, Pomari C, Picece V, Gori S
Drug Target Insights
· 2023 · PMID 37840886
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Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene () exon 14 skipping mutation has not been established yet. MET inhibitors were demonstrated to be effective...Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene () exon 14 skipping mutation has not been established yet. MET inhibitors were demonstrated to be effective and tolerated in patients with this condition, while evidence on safety and efficacy of immunotherapy and/or chemotherapy in this population is limited. Here we report the case of an 86-year-old male with metastatic NSCLC harboring exon 14 skipping mutation and with high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score ≥50%). The patient received the MET inhibitor tepotinib as first-line treatment, achieving a partial response, with G2 peripheral edema as adverse event that was successfully managed with temporary discontinuation, dose reduction, diuretics and physical therapy. After 31 months, the patient is still receiving tepotinib, with an ongoing response. Tepotinib is a valuable therapeutic option for first-line treatment of older patients with NSCLC harboring exon 14 skipping mutation, even in the presence of high PD-L1 expression.
Drug Target Insights
· 2023 · PMID 37822951
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BACKGROUND: Antibiotic misuse is a major public health issue with long-term repercussions. OBJECTIVE: The purpose of this investigation was to evaluate the effects of pneumonia and diarrhea, with an emphasis on antibioti...BACKGROUND: Antibiotic misuse is a major public health issue with long-term repercussions. OBJECTIVE: The purpose of this investigation was to evaluate the effects of pneumonia and diarrhea, with an emphasis on antibiotic misuse. METHODOLOGY: This study included 410 participants (217 fathers and 193 mothers), of whom 239 purchased antibiotics for their children without a prescription, whereas 171 had a prescription or were unsure if one was required. RESULTS: Antibiotics were used incorrectly by 58.1% of respondents. About 51.2% of participants said they were taking two antibiotics at the same time. Around 30% of people admitted to using antibiotics inefficiently. The most prevalent reason for use was "viral and bacterial," followed by "viral," and then "bacterial," with 35%, 21%, and 20%, respectively. In addition, 22.4% of patients have used antibiotics for an unknown reason. CONCLUSION: Saudi parents of children with pneumonia and diarrhea abuse antibiotics. Saudi legislation banning medications without a prescription has helped reduce antibiotic abuse, but more community-based education and awareness are needed.
Drug Target Insights
· 2023 · PMID 37811195
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INTRODUCTION: Antibiotic-resistant strains cause considerable morbidity and mortality globally. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathog...INTRODUCTION: Antibiotic-resistant strains cause considerable morbidity and mortality globally. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents against it. This study attempted to identify small-molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) in . 'Las' system can be said to be the 'master' regulator of quorum sensing in , whose receptor protein is LasR. Similarly, NOR is crucial to detoxification of reactive nitrogen species. METHODS: identification of potential LasR or NOR inhibitors was attempted through a virtual screening platform AtomNet® to obtain a final subset of <100 top scoring compounds. These compounds were evaluated for their anti-pathogenic activity by challenging the model host with in the presence or absence of test compounds. Survival of the worm population in 24-well assay plates was monitored over a period of 5 days microscopically. RESULTS: Of the 96 predicted LasR inhibitors, 11 exhibited anti- activity (23%-96% inhibition of bacterial virulence as per third-day end-point) at 25-50 µg/mL. Of the 85 predicted NOR inhibitors, 8 exhibited anti- activity (40%-85% inhibition of bacterial virulence as per second-day end-point) at 25-50 µg/mL. CONCLUSION: Further investigation on molecular mode of action of compounds found active in this study is warranted. Virtual screening can be said to be a useful tool in narrowing down the list of compounds requiring actual wet-lab screening, saving considerable time and efforts for drug discovery.
Kalambry AC, Potindji TMF, Guindo I
… +6 more, Kassogue A, Drame BSI, Togo S, Yena S, Doumbia S, Diakite M
Drug Target Insights
· 2023 · PMID 37654725
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BACKGROUND: Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum β-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa,...BACKGROUND: Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum β-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa, complicated by AMR. This study aimed to investigate the prevalence and molecular characteristics of ESBL and carbapenemase-producing enterobacteria in pleural effusions in Mali. MATERIALS AND METHODS: Pleural fluid samples from 526 patients with pleuritis were analyzed. Enterobacterial species were isolated and identified, and the prevalence of resistance genes () and virulence factors was determined. RESULTS: Among the patients, 110 were diagnosed with enterobacterial pleuritis. were the main pathogens identified. Resistance to β-lactams and cephalosporins was high, while carbapenems showed good activity. ESBL production was detected in 33.6% of isolates, with being the most common gene. Carbapenemase gene () was found in three isolates. CONCLUSION: The study highlights the high prevalence of multidrug-resistant bacteria and the need for appropriate antibiotic selection based on local resistance patterns. Understanding the molecular characteristics of resistance is crucial for optimizing patient care and developing effective therapeutic strategies. Further research is needed to monitor and control AMR in PIs in Mali.
Inno A, Marchetti F, Valerio M
… +4 more, Giaj Levra N, Alongi F, Foti G, Gori S
Drug Target Insights
· 2023 · PMID 37408855
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In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients wi...In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients with untreated and/or active brain metastases were excluded from the trial, and the activity of sotorasib in the setting of brain metastases should be further investigated. Here we report the case of a KRAS p.G12C mutant NSCLC patient with three brain metastases, of whom one was untreated and the other two had progressed after radiotherapy with symptoms requiring steroids, that responded to sotorasib. Our report suggests that sotorasib may be active against untreated or progressive brain metastases, supporting further evaluation of sotorasib in this setting.
Drug Target Insights
· 2023 · PMID 37304408
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BACKGROUND: Tuberculosis (TB) mains a deadly disease affecting one-third population globally. Long turnaround time and poor sensitivity of the conventional diagnostics are the major impediments for faster diagnosis of t...BACKGROUND: Tuberculosis (TB) mains a deadly disease affecting one-third population globally. Long turnaround time and poor sensitivity of the conventional diagnostics are the major impediments for faster diagnosis of to prevent drug resistance. To overcome these issues, molecular diagnostics have been developed. They offer enhanced sensitivity but require sophisticated infrastructure, skilled manpower and remain expensive. METHODS: In that context, loop-mediated isothermal amplification (LAMP) assay, recommended by the WHO in 2016 for TB diagnosis, sounds as a promising alternative that facilitates visual read outs. Therefore, the aim of the present study is to conduct a meta-analysis to assess the diagnostic efficiency of LAMP for the detection of a panel of . following PRISMA guidelines using scientific databases. From 1600 studies reported on the diagnosis of ., a selection of 30 articles were identified as eligible to meet the criteria of LAMP based diagnosis. RESULTS: It was found that most of the studies were conducted in high disease burden nations such as India, Thailand, and Japan with sputum as the most common specimen to be used for LAMP assay. Furthermore, gene and fluorescence-based detections ranked as the most used target and method respectively. The accuracy and precision rates mostly varied between 79.2% to 99.3% and 73.9% to 100%, respectively. Lastly, a quality assessment based on QUADAS-2 of bias and applicability was conducted. CONCLUSION: LAMP technology could be considered as a feasible alternative to current diagnostics considering high burden for rapid testing in low resource regions.
Khan SF, Shetty B, Fazal I
… +5 more, Khan AM, Mir FM, Moothedath M, Reshma VJ, Muhamood M
Drug Target Insights
· 2023 · PMID 37288311
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Periodontal disease is caused by specific pathogens which results in inflammation of the tooth-supporting structures and subsequently causes the continued breakdown of alveolar bone and periodontal ligament. Licorice ()...Periodontal disease is caused by specific pathogens which results in inflammation of the tooth-supporting structures and subsequently causes the continued breakdown of alveolar bone and periodontal ligament. Licorice () is a perennial herb with substantial medicinal value. Licorice extract is derived from dried, unpeeled stolons and roots of and . The bioactive ingredients in licorice extract such as glycyrrhizin, licoricidin, glabridin, licochalcone A, and licorisoflavan A have anti-inflammatory, antimicrobial, and anti-adherence effects that are beneficial against periodontal disease. Since periodontal disease has a complex etiology that includes the host response and microorganisms, licorice phytochemicals offer a therapeutic advantage due to their dual functionality. The aim of this review was to enumerate the bioactive compounds present in herbal licorice extract and to elucidate the beneficial effects of licorice and its derivatives in periodontal therapy. Literature review and clinical trials evaluating the effect of licorice on periodontopathogens and periodontal disease are included in this article.
Ruparel FJ, Shah SK, Patel JH
… +3 more, Thakkar NR, Gajera GN, Kothari VO
Drug Target Insights
· 2023 · PMID 37275512
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INTRODUCTION: Antimicrobial resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help antimicrobial drug discovery programs. This study attempted identificat...INTRODUCTION: Antimicrobial resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help antimicrobial drug discovery programs. This study attempted identification of potential targets in two important pathogens and METHODS: Transcriptomes of and exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets. RESULTS: Genes associated with denitrification and sulfur metabolism emerged as the most important targets in . Increased buildup of nitrite (NO) in culture exposed to the polyherbal formulation was confirmed through assay too. Generation of nitrosative stress and inducing sulfur starvation seemed to be effective anti-pathogenic strategies against this notorious gram-negative pathogen. Important targets identified in were the transcriptional regulator , immunoglobulin-binding protein Sbi, serine protease , the response regulator system, and gamma-hemolysin components and . CONCLUSION: Further validation of the potential targets identified in this study is warranted through appropriate and assays in model hosts. Such validated targets can prove vital to many antibacterial drug discovery programs globally.
Rattanathanoo R, Chindaprasirt J, Boonsawat W
… +3 more, Limpawattana P, Khamsai S, Sawanyawisuth K
Drug Target Insights
· 2023 · PMID 37228574
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BACKGROUND:: Calcium channel blocker (CCB) is a common antihypertensive agent for the treatment of hypertension. There are inconsistent data of an association of CCB and lung cancer in the literature. This study aimed to...BACKGROUND:: Calcium channel blocker (CCB) is a common antihypertensive agent for the treatment of hypertension. There are inconsistent data of an association of CCB and lung cancer in the literature. This study aimed to evaluate this association by a case-control design. METHODS:: The inclusion criteria were adult patients 18 years or over, diagnosed with hypertension, lung cancer or pulmonary tuberculosis, and presenting with one of the suggestive symptoms of lung cancer. Those who were pregnant or had a diagnosis of lung cancer or pulmonary tuberculosis prior to the diagnosis of hypertension were excluded. Diagnosis of lung cancer was made pathologically, while tuberculosis was made by positive acid-fast bacilli on sputum examination, sputum culture positive for , or polymerase chain reaction positive for with a chest x-ray compatible with tuberculosis. Cases were those diagnosed with lung cancer, while controls were those diagnosed with tuberculosis. Factors associated with lung cancer were calculated by logistic regression analysis. RESULTS:: There were 178 patients who met the study criteria. Of those, 69 patients (38.8%) were in the case group. The lung cancer group had gene mutation in 21 patients (52.5%) and adenocarcinoma was the most common cell type of lung cancer (55 patients; 79.7%). There were two factors independently associated with lung cancer including dyslipidemia and family history of lung cancer. CONCLUSIONS:: CCB was not associated with lung cancer in patients with hypertension but dyslipidemia and family history of lung cancer were independently associated with lung cancer in this setting.
Khemla S, Meesing A, Sribenjalux W
… +1 more, Chetchotisakd P
Drug Target Insights
· 2023 · PMID 37153647
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INTRODUCTION:: Human immunodeficiency virus (HIV) infection and the long-term use of antiretroviral therapy, especially efavirenz (EFV)-based regimens, impact lipid profiles due to insulin resistance and lead to a higher...INTRODUCTION:: Human immunodeficiency virus (HIV) infection and the long-term use of antiretroviral therapy, especially efavirenz (EFV)-based regimens, impact lipid profiles due to insulin resistance and lead to a higher risk of metabolic diseases. Dolutegravir (DTG) is an integrase inhibitor with better lipid profiles than EFV. However, data on treatment experience in Thailand are limited. The primary outcome was lipid profile changes at 24 weeks after switching therapy. METHODS:: We conducted a prospective, open-label, cohort study in people with HIV aged ≥18 years who had undergone at least 6 months of EFV-based therapy, had HIV-1 ribonucleic acid levels <50 copies/mL for ≥6 months before switching, and were diagnosed with dyslipidemia or had risk factors for atherosclerosis cardiovascular disease based on modified National Cholesterol Education Program Adult Treatment Panel III guidelines. RESULTS:: Sixty-four patients were enrolled. The mean age (standard deviation [SD]) was 48.20 ± 10.46 years, and 67.19% were male. At week 24, there were decreases from baseline in mean total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. However, mean body weight and waist circumference had increased. CONCLUSIONS:: DTG resulted in better lipid profiles after switching from EFV-based therapy, suggesting that this switch could benefit patients with a high risk of cardiovascular disease. However, it is essential to note that weight gain and increased waist circumference were also observed.
Zambelli V, Murphy EJ, Delvecchio P
… +4 more, Rizzi L, Fumagalli R, Rezoagli E, Bellani G
Drug Target Insights
· 2023 · PMID 37070031
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INTRODUCTION: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer wide...INTRODUCTION: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability. METHODS: Sprague-Dawley rats underwent prolonged MV (5 hours). VIDD+Levo group received a starting bolus of levosimendan immediately after intratracheal intubation and then an intravenous infusion of levosimendan throughout the study. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis and Western blot analysis. Healthy rats were used as the control. RESULTS: Levosimendan treatment maintained an adequate mean arterial pressure during the entire experimental protocol, preserved levels of autophagy-related proteins (LC3BI and LC3BII) and the muscular cell diameter demonstrated by histological analysis. Levosimendan did not affect the diaphragmatic contraction or the levels of proteins involved in the protein degradation (atrogin). CONCLUSIONS: Our data suggest that levosimendan preserves muscular cell structure (cross-sectional area) and muscle autophagy after 5 hours of MV in a rat model of VIDD. However, levosimendan did not improve diaphragm contractile efficiency.
Shetty B, Fazal I, Khan SF
… +4 more, Nambiar M, D KI, Prasad R, Raj A
Drug Target Insights
· 2023 · PMID 36761891
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Cardiovascular diseases (CVDs) are inflammatory diseases of coronary arteries accompanying atheroma formation that can spawn impairment and, in severe cases, death. CVDs are the leading cause of death in the world. In re...Cardiovascular diseases (CVDs) are inflammatory diseases of coronary arteries accompanying atheroma formation that can spawn impairment and, in severe cases, death. CVDs are the leading cause of death in the world. In recent decades, investigators have focused their impact on CVD by periodontal disease (PD). PD is a risk factor that can trigger the formation, maturation, and instability of atheroma in the arteries. Two mechanisms have been proposed to explain this relationship: periodontopathic pathogens explicitly invade the circulation or indirectly increase systemic levels of inflammatory mediators. It has been suggested that improvement in disease state has a positive effect on others. This review summarizes evidence from epidemiological studies as well as researches focusing on potential causation channels to deliver a comprehensive representation of the relationship between PD and CVD.