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1.
Nanoscale Adv ; 6(12): 3239, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38868833

ABSTRACT

[This retracts the article DOI: 10.1039/D1NA00214G.].

2.
Infection ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856808

ABSTRACT

BACKGROUND: The landscape of Pseudomonas infective endocarditis (IE) is evolving with the widespread use of cardiac implantable devices and hospital-acquired infections. This systematic review aimed to evaluate the emerging risk factors and outcomes in Pseudomonas IE. METHODS: A literature search was performed in major electronic databases (PubMed, Scopus, and Google Scholar) with appropriate keywords and combinations till November 2023. We recorded data for risk factors, diagnostic and treatment modalities. This study is registered with PROSPERO, CRD42023442807. RESULTS: A total of 218 cases (131 articles) were included. Intravenous drug use (IDUs) and prosthetic valve endocarditis (PVE) were major risk factors for IE (37.6% and 22%). However, the prosthetic valve was the predominant risk factor in the last two decades (23.5%). Paravalvular complications (paravalvular leak, abscess, or pseudoaneurysm) were described in 40 cases (18%), and the vast majority belonged to the aortic valve (70%). The mean time from symptom onset to presentation was 14 days. The incidence of difficult-to-treat resistant (DTR) pseudomonas was 7.4%. Valve replacement was performed in 57.3% of cases. Combination antibiotics were used in most cases (77%), with the aminoglycosides-based combination being the most frequently used (66%). The overall mortality rate was 26.1%. The recurrence rate was 11.2%. Almost half of these patients were IDUs (47%), and most had aortic valve endocarditis (76%). CONCLUSIONS: This review highlights the changing epidemiology of Pseudomonas endocarditis with the emergence of prosthetic valve infections. Acute presentation and associated high mortality are characteristic of Pseudomonas IE and require aggressive diagnostic and therapeutic approach.

3.
Vet Res Commun ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829518

ABSTRACT

Somatic cell nuclear transfer (SCNT) is a very important reproductive technology with many diverse applications, such as fast multiplication of elite animals, the production of transgenic animals and embryonic stem (ES) cells. However, low cloning efficiency, a low live birth rate and the abnormally high incidence of abnormalities in the offspring born are attributed to incomplete or aberrant nuclear reprogramming. In SCNT embryos, the aberrant expression pattern of the genes throughout embryonic development is responsible for the incomplete nuclear reprogramming. The present study was carried out to identify the differential gene expression (DEGs) profile and molecular pathways of the SCNT and IVF embryos at different developmental stages (2 cell, 8 cell and blastocyst stages). In the present study, 1164 (2 cell), 1004 (8 cell) and 530 (blastocyst stage) DEGs were identified in the SCNT embryos as compared to IVF embryos. In addition, several genes such as ZEB1, GDF1, HSF5, PDE3B, VIM, TNNC, HSD3B1, TAGLN, ITGA4 and AGMAT were affecting the development of SCNT embryos as compared to IVF embryos. Further, Gene Ontology (GO) and molecular pathways analysis suggested, SCNT embryos exhibit variations compared to their IVF counterparts and affected the development of embryos throughout the different developmental stages. Apart from this, q-PCR analysis of the GDF1, TMEM114, and IGSF22 genes were utilized to validate the RNA-seq data. These findings contribute valuable insights about the different genes and molecular pathways underlying SCNT embryo development and offer crucial information for improving SCNT efficiency.

4.
J Clin Immunol ; 44(7): 153, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896122

ABSTRACT

Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.


Subject(s)
Epstein-Barr Virus Infections , Hodgkin Disease , Lymphohistiocytosis, Hemophagocytic , Humans , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/genetics , Male , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/genetics , Hodgkin Disease/diagnosis , Hodgkin Disease/genetics , Hodgkin Disease/etiology , Herpesvirus 4, Human , Recurrence , Hematopoietic Stem Cell Transplantation , Cation Transport Proteins
5.
World J Orthop ; 15(5): 486-488, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38835683

ABSTRACT

We read and discussed the study entitled "Complication rates after direct anterior vs posterior approach for Hip Hemiarthroplasty in elderly individuals with femoral neck fractures" with great interest. The authors have done justice to the topic of comparison of anterior and posterior surgical approaches for bipolar hemiarthroplasty which has been an everlasting debate in the existing literature. However, there are certain aspects of this study that need clarification from the authors.

6.
Mini Rev Med Chem ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38859778

ABSTRACT

Cancer remains a primary cause of death globally, and effective treatments are still limited. While chemotherapy has notably enhanced survival rates, it brings about numerous side effects. Consequently, the ongoing challenge persists in developing potent anti-cancer agents with minimal toxicity. The versatile nature of the quinazoline moiety has positioned it as a pivotal component in the development of various antitumor agents, showcasing its promising role in innovative cancer therapeutics. This concise review aims to reveal the potential of quinazolines in creating anticancer medications that target histone deacetylases (HDACs).

8.
Ann Med Surg (Lond) ; 86(6): 3551-3556, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846885

ABSTRACT

ECG changes in pneumothorax have gained recognition as important indicators of cardiopulmonary interactions. This narrative review examines the existing literature to provide insights into the various ECG abnormalities observed in patients with pneumothorax, their underlying mechanisms, and clinical implications. The review highlights the commonly reported changes, including alterations in the electrical axis, ST segment deviations, T-wave abnormalities, and arrhythmias. The rightward shift of the electrical axis is attributed to cardiac displacement caused by increased intrathoracic pressure. ST segment deviations may reflect the influence of altered intrathoracic pressure on myocardial oxygen supply and demand. T-wave abnormalities may result from altered myocardial repolarization and hypoxemia. Arrhythmias, although varying in incidence and type, have been associated with pneumothorax. The clinical implications of these ECG changes are discussed, emphasizing their role in diagnosis, risk stratification, treatment optimization, and prognostication. Additionally, future research directions are outlined, including prospective studies, mechanistic investigations, and the integration of artificial intelligence. Enhancing our understanding of ECG changes in pneumothorax can lead to improved patient care, better management strategies, and the development of evidence-based guidelines. The objective of this review is to demonstrate the presence of various ECG abnormalities in patients with pneumothorax.

9.
Mol Ther Nucleic Acids ; 35(2): 102202, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38846999

ABSTRACT

Splicing factor 3b subunit 1 (SF3B1) is the largest subunit and core component of the spliceosome. Inhibition of SF3B1 was associated with an increase in broad intron retention (IR) on most transcripts, suggesting that IR can be used as a marker of spliceosome inhibition in chronic lymphocytic leukemia (CLL) cells. Furthermore, we separately analyzed exonic and intronic mapped reads on annotated RNA-sequencing transcripts obtained from B cells (n = 98 CLL patients) and healthy volunteers (n = 9). We measured intron/exon ratio to use that as a surrogate for alternative RNA splicing (ARS) and found that 66% of CLL-B cell transcripts had significant IR elevation compared with normal B cells (NBCs) and that correlated with mRNA downregulation and low expression levels. Transcripts with the highest IR levels belonged to biological pathways associated with gene expression and RNA splicing. A >2-fold increase of active pSF3B1 was observed in CLL-B cells compared with NBCs. Additionally, when the CLL-B cells were treated with macrolides (pladienolide-B), a significant decrease in pSF3B1, but not total SF3B1 protein, was observed. These findings suggest that IR/ARS is increased in CLL, which is associated with SF3B1 phosphorylation and susceptibility to SF3B1 inhibitors. These data provide additional support to the relevance of ARS in carcinogenesis and evidence of pSF3B1 participation in this process.

10.
Med Oncol ; 41(7): 164, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816663

ABSTRACT

The Wnt/ß-Catenin pathway (Wnt/ß-CatP) is implicated in accelerating carcinogenesis and cancer progression, contributing to increased morbidity and treatment resistance. Even though it holds promise as a focus for cancer treatment, its intricate nature and diverse physiological effects pose significant challenges. Recent years have witnessed significant advancements in this domain, with numerous natural products demonstrating promising preclinical anti-tumor effects and identified as inhibitors of the Wnt/ß-CatP through various upstream and downstream mechanisms. This study provides a comprehensive overview of the current landscape of Wnt/ß-Cat-targeted cancer therapy, examining the impact of natural products on Wnt/ß-Cat signaling in both cancer prevention and therapeutic contexts. A comprehensive search was conducted on scientific databases like SciFinder, PubMed, and Google Scholar to retrieve relevant literature on Wnt-signaling, natural products, ß-Catenin (ß-Cat), and cancer from 2020 to January 2024. As per the analysis of the relevant reference within the specified period, it has been noted that a total of 58 phytoconstituents, predominantly phenolics, followed by triterpenoids and several other classes, along with a limited number of plant extracts, have exhibited activity targeting the Wnt/ß-CatP. Most ß-Cat regulating modulators restrict cancer cell development by suppressing ß-Cat expression, facilitating proteasomal degradation, and inhibiting nuclear translocation. Multiple approaches have been devised to block the activity of ß-Cat in cancer therapy, a key factor in cancer progression, leading to the discovery of various Wnt/ß-CatP regulators. However, their exploration remains limited, necessitating further research using clinical models for potential clinical use in cancer prevention and therapeutics.


Subject(s)
Biological Products , Neoplasms , Wnt Signaling Pathway , Humans , Biological Products/therapeutic use , Biological Products/pharmacology , Neoplasms/drug therapy , Neoplasms/prevention & control , Neoplasms/metabolism , Wnt Signaling Pathway/drug effects , beta Catenin/metabolism , Animals
11.
Luminescence ; 39(5): e4771, 2024 May.
Article in English | MEDLINE | ID: mdl-38747206

ABSTRACT

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.


Subject(s)
Chalcogens , Neoplasms , Transition Elements , Humans , Neoplasms/drug therapy , Transition Elements/chemistry , Chalcogens/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Animals
12.
Plant Physiol Biochem ; 212: 108731, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761545

ABSTRACT

Seed endophytic bacteria have been shown to promote the growth and development of numerous plants. However, the underlying mechanism still needs to be better understood. The present study aims to investigate the role of a seed endophytic bacterium Lysinibacillus sp. (ZM1) in promoting plant growth and shaping the root architecture of maize seedlings. The study explores how bacteria-mediated auxin biosynthesis and nitrogen metabolism affect plant growth promotion and shape the root architecture of maize seedlings. The results demonstrate that ZM1 inoculation significantly enhances root length, root biomass, and the number of seminal roots in maize seedlings. Additionally, the treated seedlings exhibit increased shoot biomass and higher levels of photosynthetic pigments. Confocal laser scanning microscopy (CLSM) analysis revealed extensive colonization of ZM1 on root hairs, as well as in the cortical and stellar regions of the root. Furthermore, LC-MS analysis demonstrated elevated auxin content in the roots of the ZM1 treated maize seedlings compared to the uninoculated control. Inoculation with ZM1 significantly increased the levels of endogenous ammonium content, GS, and GOGAT enzyme activities in the roots of treated maize seedlings compared to the control, indicating enhanced nitrogen metabolism. Furthermore, inoculation of bacteria under nitrogen-deficient conditions enhanced plant growth, as evidenced by increased root shoot length, fresh and dry weights, average number of seminal roots, and content of photosynthetic pigments. Transcript analysis indicated upregulation of auxin biosynthetic genes, along with genes involved in nitrogen metabolism at different time points in roots of ZM1-treated maize seedlings. Collectively, our findings highlight the positive impact of Lysinibacillus sp. ZM1 inoculation on maize seeds by improving root architecture through modulation of auxin biosynthesis and affecting various nitrogen metabolism related parameters. These findings provide valuable insights into the potential utilization of seed endophytic bacteria as biofertilizers to enhance plant growth and yield in nutrient deficient soils.


Subject(s)
Bacillaceae , Indoleacetic Acids , Nitrogen , Plant Roots , Zea mays , Zea mays/microbiology , Zea mays/metabolism , Zea mays/growth & development , Indoleacetic Acids/metabolism , Nitrogen/metabolism , Plant Roots/microbiology , Plant Roots/metabolism , Bacillaceae/metabolism , Endophytes/metabolism , Endophytes/physiology , Seeds/microbiology , Seeds/metabolism , Seeds/growth & development , Seedlings/microbiology , Seedlings/metabolism , Seedlings/growth & development
13.
Article in English | MEDLINE | ID: mdl-38763431

ABSTRACT

OBJECTIVE: Individuals with chronic pain due to knee osteoarthritis (OA) are insufficiently physically active, and alterations of facilitatory and inhibitory nociceptive signaling are common in this population. Our objective was to examine the association of these alterations in nociceptive signaling with objective accelerometer-based measures of physical activity in a large observational cohort. DESIGN: We used data from the Multicenter Osteoarthritis Study. Measures of peripheral and central pain sensitivity included pressure pain threshold at the knee and mechanical temporal summation at the wrist, respectively. The presence of descending pain inhibition was assessed by conditioned pain modulation (CPM). Physical activity was quantitatively assessed over 7 days using a lower back-worn activity monitor. Summary metrics included steps/day, activity intensity, and sedentary time. Linear regression analyses were used to evaluate the association of pain sensitivity and the presence of descending pain inhibition with physical activity measures. RESULTS: Data from 1873 participants was analyzed (55.9% female, age = 62.8 ± 10.0 years). People having greater peripheral and central sensitivity showed lower step counts. CPM was not significantly related to any of the physical activity measures, and none of the exposures were significantly related to sedentary time. CONCLUSIONS: In this cohort, greater peripheral and central sensitivity were associated with reduced levels of objectively-assessed daily step counts. Further research may investigate ways to modify or treat heightened pain sensitivity as a means to increase physical activity in older adults with knee OA.

15.
bioRxiv ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38765993

ABSTRACT

Background: MicroRNAs (miRNAs) represent a subset of small noncoding RNAs and carry tremendous potential for regulating gene expression at the post-transcriptional level. They play pivotal roles in distinct cellular mechanisms including inhibition of bacterial, parasitic, and viral infections via immune response pathways. Intriguingly, pathogens have developed strategies to manipulate the host's miRNA profile, fostering environments conducive to successful infection. Therefore, changes in an arthropod host's miRNA profile in response to pathogen invasion could be critical in understanding host-pathogen dynamics. Additionally, this area of study could provide insights into discovering new targets for disease control and prevention. The main objective of the present study is to investigate the functional role of differentially expressed miRNAs upon Ehrlichia chaffeensis, a tick-borne pathogen, infection in tick vector, Amblyomma americanum. Methods: Small RNA libraries from uninfected and E. chaffeensis-infected Am. americanum midgut and salivary gland tissues were prepared using the Illumina Truseq kit. Small RNA sequencing data was analyzed using miRDeep2 and sRNAtoolbox to identify novel and known miRNAs. The differentially expressed miRNAs were validated using a quantitative PCR assay. Furthermore, a miRNA inhibitor approach was used to determine the functional role of selected miRNA candidates. Results: The sequencing of small RNA libraries generated >147 million raw reads in all four libraries and identified a total of >250 miRNAs across the four libraries. We identified 23 and 14 differentially expressed miRNAs in salivary glands, and midgut tissues infected with E. chaffeensis, respectively. Three differentially expressed miRNAs (miR-87, miR-750, and miR-275) were further characterized to determine their roles in pathogen infection. Inhibition of target miRNAs significantly decreased the E. chaffeensis load in tick tissues, which warrants more in-depth mechanistic studies. Conclusions: The current study identified known and novel miRNAs and suggests that interfering with these miRNAs may impact the vectorial capacity of ticks to harbor Ehrlichia. This study identified several new miRNAs for future analysis of their functions in tick biology and tick-pathogen interaction studies.

16.
Heliyon ; 10(10): e31232, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813207

ABSTRACT

Gangetic old alluvial zone in India has conserved many locally adapted aromatic rice landraces. In order to determine the extent of genetic divergence of ten morphological characters, the study was conducted to examine forty-eight aromatic rice genotypes for six Kharif seasons (2016-2021) at the Instructional Farm of Regional Research Station (Old Alluvial Zone), Uttar Banga Krishi Viswavidyalaya, Majhian, West Bengal, India. The experiment was laid out in Randomized Complete Block Design (RCBD) with three replications. A considerable degree of variation was noted for all the traits being investigated. It was found that the total number of tillers per plant, panicle numbers per plant, number of grains per panicle, fertility percentage, test weight, and grain length/breadth ratio had significantly positive correlated with seed yield per plant. Based on D2 analysis values, all the genotypes were grouped into six clusters. Cluster III (Tulaipanji, Patnai, Basmati 1121, Jugal, and Bahurupi) and Cluster VI (Kanakchur), containing genotypes were found most divergent with maximum inter-cluster distance (6941.51). According to the cluster means, Cluster II had the largest intra-cluster distance (1937.52), and important attributes including test weight, number of grains per panicle, seed yield per plant, and fertility percentage made remarkably significant contributions to this cluster. In terms of principal component analysis, maximum variability was found in PC1 (23.88 %), with high positive loading values for tillers per plant (0.459), panicle number per plant (0.441), seed yield per plant (0.408), fertility percentage (0.364), test weight (0.264), and grain length/breadth (L/B) ratio (0.263). On the basis of biplot analysis, four genotypes, namely Shakbhati, Sugandhi, Bahurupi and Kanakchur, were identified as the most divergent types for the yield-attributing traits of aromatic rice. The diverse genotypes could be used as potential donors in future breeding programmes.

17.
Maedica (Bucur) ; 19(1): 170-176, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38736930

ABSTRACT

Malignant solitary fibrous tumor of the breast is one of the rarest types of breast malignancy. To the best of our knowledge, only six cases have been reported so far. Here we have presented such a case from India, where a 52-year-old lady presented with a 10 cm x 8 cm breast lump. Diagnosis was achieved with the help of FDG PET, histopathology and immunohistochemistry, which showed nuclear positivity for STAT6. Fluorescent in situ hybridization (FISH) molecular study for SS18-SSX was used to rule out the differential diagnosis of synovial sarcoma. Guidelines for the management of this type of breast malignancy still do not exist. We have done a review of the literature in order to discuss which might be the best management in such cases. Evidence on this very rarest type of breast malignancy is still evolving. The interest in the case described here relies on its rarity, difficulties in achieving diagnosis and formulation of the proper management.

18.
J Neurosci Rural Pract ; 15(2): 262-269, 2024.
Article in English | MEDLINE | ID: mdl-38746516

ABSTRACT

Objectives: IMPUTE Inc., a software firm dedicated to healthcare technology, has developed a mobile medical application known as IMPUTE ADT-1 for children with autism spectrum disorder (ASD) based on the principle of applied behavior analysis. Materials and Methods: The primary objective of this trial was to compare the efficacy of add-on treatment with IMPUTE ADT-1 in children with ASD aged two to six years as compared to standard care alone for 12 weeks (in terms of change in Autism Diagnostic Observation Schedule [ADOS-2] scores). The secondary objective of the study was to assess the compliance with IMPUTE ADT-1 among participants and also to evaluate the feedback of parents regarding IMPUTE ADT-1 at the end of 12 weeks. The application provides personalized programs tailored to each user's needs, and the program evolves based on the user's progress. It also utilizes face tracking, eye tracking, and body tracking to gather behavior-related information for each child and apply it in reinforcement learning employing artificial intelligence-based algorithms. Results: Till the time of interim analysis, 37 and 33 children had completed 12-week follow-up in IMPUTE ADT-1 and control arm. At 12 weeks, as compared to baseline, change in social affect domain, repetitive ritualistic behavior domain, total ADOS-2 score, and ADOS-2 comparison score was better in the intervention group as compared to the control group (P < 0.001 for all). A total of 30 (81%), 28 (75%), and 29 (78%) caregivers in the IMPUTE ADT-1 group believed that the ADT-1 app improved their child's verbal skills, social skills, and reduced repetitive behavior, respectively. Conclusion: IMPUTE ADT-1 mobile application has the efficacy to improve the severity of autism symptoms in children. Parents of these children also feel that the application is beneficial for improving the socialization and verbal communication of their children.

19.
iScience ; 27(5): 109768, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38711441

ABSTRACT

Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5'-UTR/non-coding region of PPP2R2B. Molecular pathology of SCA12 has not been studied in the context of CAG repeats, and no appropriate models exist. We found in human SCA12-iPSC-derived neuronal lineage that expanded CAG in PPP2R2B transcript forms nuclear RNA foci and were found to sequester variety of proteins. Further, the ectopic expression of transcript containing varying length of CAG repeats exhibits non-canonical repeat-associated non-AUG (RAN) translation in multiple frames in HEK293T cells, which was further validated in patient-derived neural stem cells using specific antibodies. mRNA sequencing of the SCA12 and control neurons have shown a network of crucial transcription factors affecting neural fate, in addition to alteration of various signaling pathways involved in neurodevelopment. Altogether, this study identifies the molecular signatures of SCA12 disorder using patient-derived neuronal cell lines.

20.
J Phys Chem B ; 128(20): 4911-4921, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38736363

ABSTRACT

To combat surging multidrug-resistant Gram-negative bacterial infections, better strategies to improve the efficacy of existing drugs are critical. Because the dual membrane cell envelope is the first line of defense for these bacteria, it is crucial to understand the permeation properties of the drugs through it. Our recent study shows that isosmotic conditions prevent drug permeation inside Gram-negative bacteria, Escherichia coli, while hypoosmotic stress enhances the process. Here, we unravel the reason behind such differential drug penetration. Specifically, we dissect the roles of electrostatic screening and low membrane permeability in the penetration failure of drugs under osmotically balanced conditions. We compare the transport of a quaternary ammonium compound malachite green in the presence of an electrolyte (NaCl) and a wide variety of commonly used organic osmolytes, e.g., sucrose, proline, glycerol, sorbitol, and urea. These osmolytes of different membrane permeability (i.e., nonpermeable sucrose and NaCl, freely permeable urea and glycerol, and partially permeable proline and sorbitol) clarify the role of osmotic stress in cell envelope permeability. The results showcase that under balanced osmotic conditions, drug molecules fail to penetrate inside E. coli cells because of low membrane permeabilities and not because of electrostatic screening imposed by the osmolytes. Contribution of the electrostatic interactions, however, cannot be completely overruled as at osmotically imbalanced conditions, drug transport across the bacterial subcellular compartments is found to be dependent on the osmolytes used.


Subject(s)
Cell Membrane Permeability , Escherichia coli , Osmotic Pressure , Static Electricity , Escherichia coli/drug effects , Escherichia coli/metabolism , Biological Transport , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Cell Membrane/metabolism , Cell Membrane/chemistry
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