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Frontiers in Bioscience (Landmark... May 2024Phosphine resistance in challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in...
BACKGROUND
Phosphine resistance in challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in Indian Tribolium castaneum populations.
METHODS
Seven field populations of were compared with Lab- susceptible population for their resistance to phosphine. The levels of cytochrome P450 enzyme and expression of certain CYP346 family genes were tracked in these populations.
RESULTS
The highly resistant Patiala population showed significantly increased CYP450 activity (11.26 ± 0.14 nmol/min/mg protein, 7.41-fold higher) compared to the lab-susceptible population (1.52 ± 0.09 nmol/min/mg protein) when assayed using 8 mM p-nitroanisole as the substrate. The mRNA expression was measured relative to the standard gene and revealed significant upregulation of and in highly resistant populations Moga and Patiala (: 12.09 ± 2.19 to 21.74 ± 3.82; : 59.097 ± 10.265 to 50.148 ± 8.272). Patiala's exhibited an impressive 685.76-fold change, and Moga's showed a 361.893-fold change compared to lab-susceptible. Linear regression confirmed robust fits for each gene (R2: 0.693 to 0.756). Principal component analysis (PCA) demonstrated a strong positive correlation between genes expression; and cytochrome P450 activity. Patiala, Moga, and Hapur populations showed conformity, associating higher resistance with increased P450 activity and CYP346 gene expression. Cluster analysis highlighted a potential correlation between , , and and P450 activity, with Patiala and Moga clustering together.
CONCLUSIONS
Variability in and in strong resistance populations may contribute to adaptation and resistance mechanisms. The study provides insights into specific CYP346 family genes associated with phosphine resistance, emphasizing the intricate interaction between CYP450 detoxifying enzymes, CYP346 family genes, and resistance mechanisms. The upregulation of genes suggests a survival advantage for against phosphine, diminishing phosphine's efficacy as a pest control measure.
Topics: Tribolium; Cytochrome P-450 Enzyme System; Insecticide Resistance; Phosphines; Insecticides; India; Animals
PubMed: 38940033
DOI: 10.31083/j.fbl2906203 -
Frontiers in Bioscience (Landmark... May 2024Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence.... (Review)
Review
Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Gastrointestinal Microbiome; Adipose Tissue, Brown; Animals; Insulin Resistance; Fecal Microbiota Transplantation; Obesity
PubMed: 38940030
DOI: 10.31083/j.fbl2906208 -
Euro Surveillance : Bulletin Europeen... Jun 2024In 2022, an outbreak with severe bloodstream infections caused by occurred in an adult intensive care unit (ICU) in Hungary. Eight cases, five of whom died, were...
In 2022, an outbreak with severe bloodstream infections caused by occurred in an adult intensive care unit (ICU) in Hungary. Eight cases, five of whom died, were detected. Initial control measures could not stop the outbreak. We conducted a matched case-control study. In univariable analysis, the cases were more likely to be located around one sink in the ICU and had more medical procedures and medications than the controls, however, the multivariable analysis was not conclusive. Isolates from blood cultures of the cases and the ICU environment were closely related by whole genome sequencing and resistant or tolerant against the quaternary ammonium compound surface disinfectant used in the ICU. Thus, was able to survive in the environment despite regular cleaning and disinfection. The hospital replaced the disinfectant with another one, tightened the cleaning protocol and strengthened hand hygiene compliance among the healthcare workers. Together, these control measures have proved effective to prevent new cases. Our results highlight the importance of multidisciplinary outbreak investigations, including environmental sampling, molecular typing and testing for disinfectant resistance.
Topics: Humans; Serratia marcescens; Disease Outbreaks; Cross Infection; Hungary; Intensive Care Units; Serratia Infections; Disinfectants; Case-Control Studies; Male; Female; Adult; Middle Aged; Whole Genome Sequencing; Disinfection; Aged; Infection Control; Drug Resistance, Bacterial
PubMed: 38940004
DOI: 10.2807/1560-7917.ES.2024.29.26.2300492 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2024As a multifunctional adipokine, chemerin plays a crucial role in various pathophysiological processes through endocrine and paracrine manner. It can bind to three known... (Review)
Review
As a multifunctional adipokine, chemerin plays a crucial role in various pathophysiological processes through endocrine and paracrine manner. It can bind to three known receptors (ChemR23, GPR1 and CCRL2) and participate in energy metabolism, glucose and lipid metabolism, and inflammation, especially in metabolic diseases. Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, which seriously affects the normal life of women of childbearing age. Patients with PCOS have significantly increased serum levels of chemerin and high expression of chemerin in their ovaries. More and more studies have shown that chemerin is involved in the occurrence and development of PCOS by affecting obesity, insulin resistance, hyperandrogenism, oxidative stress and inflammatory response. This article mainly reviews the production, subtypes, function and receptors of chemerin protein, summarizes and discusses the research status of chemerin protein in PCOS from the perspectives of metabolism, reproduction and inflammation, and provides theoretical basis and reference for the clinical diagnosis and treatment of PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Chemokines; Female; Intercellular Signaling Peptides and Proteins; Receptors, Chemokine; Insulin Resistance; Animals; Receptors, G-Protein-Coupled; Chemotactic Factors
PubMed: 38939937
DOI: No ID Found -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2024The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects...
The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects of HFD on the pathology and function of organs related to glucose and lipid metabolism. C57BL/6 mice were fed with normal diet (NC group) or HFD (HFD group). The time of successful T2DM modeling was evaluated by measuring body weight, fasting blood glucose and glucose tolerance at time points of 0, 4, 8, 12, 16 and 20 weeks. The functional and pathological changes of glucose and lipid metabolism related organs were evaluated by detecting insulin tolerance, plasma lipid levels, vascular function, as well as HE staining of pancreas and liver. The results showed that compared with the NC group, the HFD group had significantly increased body weight after 8 weeks of HFD. After 16 weeks of HFD, the HFD group exhibited impaired fasting glucose tolerance. After 20 weeks of HFD, the HFD group mice reached diabetic state, showing impaired glucose tolerance and insulin resistance, islet volume reduction and vacuolar degeneration; Large number of lipid droplets appeared in liver cells, and the level of AMPK phosphorylation in liver tissue was significantly increased in the HFD groups, compared with the NC group; There was endothelial dependent diastolic dysfunction in the thoracic aorta of the HFD group; Compared with the NC group, the HFD group mice showed a significant increase in urinary protein levels. These results suggest that T2DM mouse model can be successfully established by HFD induction alone for 20 weeks. The model is characterized by insulin resistance, fatty liver, hyperlipidemia, vascular dysfunction, renal dysfunction and pathological changes of islet and liver cells, which are similar to those of T2DM patients. Therefore it can be used as an ideal animal model for T2DM research.
Topics: Animals; Diabetes Mellitus, Type 2; Mice; Diet, High-Fat; Mice, Inbred C57BL; Male; Disease Models, Animal; Insulin Resistance; Lipid Metabolism; Diabetes Mellitus, Experimental; Liver
PubMed: 38939933
DOI: No ID Found -
Journal of Extracellular Biology Feb 2024Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell...
Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in expression in the oxaliplatin-resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta-databases, RNA levels were continually detected in colorectal tissue arrays. Additionally, protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial-type marker CDH1 was suppressed in overexpression models, whereas the expression of the mesenchymal-type markers SNAI1 and SNAI2 increased. Notably, -induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that /AGR2 axis-mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.
PubMed: 38939899
DOI: 10.1002/jex2.141 -
Journal of Extracellular Biology Oct 2023Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and...
Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and responsible for several millions of deaths. Research on extracellular vesicles (EVs) has increased in recent years and demonstrated that EVs shed by pathogenic parasites interact with host cells playing an important role in the parasite's survival, such as facilitation of infection, immunomodulation, parasite adaptation to the host environment and the transfer of drug resistance factors. Thus, EVs released by parasites mediate parasite-parasite and parasite-host intercellular communication. In addition, they are being explored as biomarkers of asymptomatic infections and disease prognosis after drug treatment. However, most current protocols used for the isolation, size determination, quantification and characterization of molecular cargo of EVs lack greater rigor, standardization, and adequate quality controls to certify the enrichment or purity of the ensuing bioproducts. We are now initiating major guidelines based on the evolution of collective knowledge in recent years. The main points covered in this position paper are methods for the isolation and molecular characterization of EVs obtained from parasite-infected cell cultures, experimental animals, and patients. The guideline also includes a discussion of suggested protocols and functional assays in host cells.
PubMed: 38939734
DOI: 10.1002/jex2.117 -
Acta Medica Philippina 2024Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for...
BACKGROUND
Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications.
OBJECTIVES
This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019.
METHODS
The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted.
RESULTS
A total of 821 patients charts met the inclusion criteria. The patients' ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days.Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were (19%), (18%), and (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials.Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommendations, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019.
CONCLUSION
Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient's perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.
PubMed: 38939423
DOI: 10.47895/amp.vi0.7249 -
Frontiers in Microbiology 2024This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics...
This study explores the prevalence of adherent-invasive (AIEC) in colorectal cancer (CRC) patients and investigates the potential of effective intracellular antibiotics as a therapeutic strategy for CRC patients with AIEC infections. Considering the pivotal role of integrons in bacterial antibiotic resistance, the frequency of class 1 and 2 integrons in AIEC isolated from CRC patients, in one of the referenced 3 gastroenterology clinics in Isfahan, Iran was examined. AIEC strains were isolated from the colorectal biopsies and their antimicrobial sensitivity was assessed using the disc diffusion method. Polymerase chain reaction (PCR) was employed to detect and . The multilocus sequence typing (MLST) method was utilized to type 10 selected isolates. Of the 150 samples, 24 were identified as AIEC, with the highest number isolated from CRC2 (33.4%) and CRC1 (29.16%), and the least from the FH group (8.3%) and control group (12.5%). in 79.2% and in 45.8% of AIEC strains were found and 41.6% of strains had both integrons. AIEC isolates with int1 exhibited the highest sensitivity to trimethoprim-sulfamethoxazole (57.9%), while those with int2 showed the highest sensitivity to ciprofloxacin (63.6%). A significant association between resistance to rifampin and integron 2 presence in AIEC isolates was observed. Furthermore, a significant correlation between integron 1 presence, invasion, survival, and replication within macrophages in AIEC strains was identified. MLST analysis revealed ST131 from CC131 with integron 1 as the most common sequence type (ST). The emergence of such strains in CRC populations poses a serious public health threat. The distribution pattern of STs varied among studied groups, with pandemic STs highlighting the importance of examining and treating patients infected with these isolates. Comprehensive prospective clinical investigations are warranted to assess the prognostic value of detecting this pathovar in CRC and to evaluate therapeutic techniques targeting drug-resistant AIECs, such as phage therapy, bacteriocins, and anti-adhesion compounds, for CRC prevention and treatment.
PubMed: 38939191
DOI: 10.3389/fmicb.2024.1366719 -
and evaluation of ethanolic crude extracts on fatty acid synthase expression on breast cancer cells.BioMedicine 2024Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This...
BACKGROUND
Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This overexpression has been affiliated with poor prognosis and resistance to chemotherapeutics. Consequently, FASN has come into focus as an appealing potential target for breast cancer treatment. Available FASN inhibitors, however, are unstable and have been correlated with adverse side effects.
OBJECTIVE
This present study aims to investigate the potential of ethanolic crude extract (AP) as a potent FASN inhibitor in breast cancer cells.
MATERIALS & METHODS
This study used MTT assay and flow cytometry analysis to measure cell viability and apoptosis following AP treatment (0-500 μg/mL). Furthermore, FASN protein expression was evaluated using immunocytochemistry whereas lipid droplet formation was quantified using Oil Red O staining. Literature-based identified AP phytochemicals were subjected to the prediction of molecular docking and ADMET properties.
RESULTS
This study demonstrated that AP significantly reduced cell viability while inducing apoptosis in breast cancer cells. In addition, for the first time, exposure to AP was demonstrated to drastically reduce intracellular FASN protein expression and lipid droplet accumulation in EMT6 and MCF-7 breast cancer cells. Docking simulation analysis demonstrated AP phytochemicals may have exerted an inhibitory effect by targeting the FASN Thioesterase (TE) domain similarly to the known FASN inhibitor, Orlistat. Moreover, all AP phytochemicals also possessed drug-likeness properties which are in accordance with Lipinski's rule of five.
CONCLUSIONS
These results highlight the potential of ethanolic crude extract as a FASN inhibitor and hence might have the potential to be further developed as a potent chemotherapeutic drug for breast cancer treatment.
PubMed: 38939097
DOI: 10.37796/2211-8039.1444