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1.
Nat Prod Res ; : 1-6, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38779992

ABSTRACT

Mosquito-borne diseases are a major public-health concern worldwide. The development of resistance in mosquitoes to the existing larvicides and the associated-risks necessitates the exploration of novel molecules to control vector-borne pathogens. This study demonstrates that N-alkylamides [2E,4E-N-isobutyl-undeca-2,4-diene-8,10-diynamide (1) and 2E,4E,8Z,10E-N-isobutyl-dodeca-2,4,8,10-tetraenamide (2)] of Acmella ciliata exhibit biocidal action against Aedes aegypti and Culex quinquefasciatus larvae. The LC50 for 1 and 2 were 44.19 and 18.28 ppm against Aedes larvae, and 30.89 and 11.75 ppm against Culex larvae, respectively. We further observed that the chain length, degree of unsaturation, and terminal methylation influence the larvicidal efficacy of N-alkylamides. HPLC-assisted quantification revealed that the content of both 1 (19.01 mg/g) and 2 (68.55 mg/g) was maximum in the flowers of A. ciliata. Thus, this study concludes that N-alkylamides are promising alternatives to control mosquito larvae and can be used as standard for quantitation in test samples.

2.
J Neurol Surg B Skull Base ; 85(3): 241-246, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38721368

ABSTRACT

Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.

4.
Infect Dis Poverty ; 13(1): 36, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783334

ABSTRACT

BACKGROUND: Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. METHODS: We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. RESULTS: Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. CONCLUSION: The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.


Subject(s)
Tuberculosis , Humans , India , Qualitative Research
5.
Cureus ; 16(4): e58789, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38784302

ABSTRACT

Cysticercosis presents a prevalent issue on a global scale. Nevertheless, disseminated cysticercosis (DCC) is infrequent; even rarer is asymptomatic DCC. Here, we present a unique case of asymptomatic DCC involving the heart in a young male who came to medical attention following a fatal snake bite, ultimately leading to his demise. Despite the widespread dissemination of cysticercosis affecting multiple organs, the individual remained asymptomatic for the condition. We present a case of a 23-year-old male who was brought to the emergency department with a history of alleged snake bites. The patient was declared dead upon arrival at the All India Institute of Medical Sciences (AIIMS), Rishikesh, India. Autopsy findings revealed multiple significant cardiac abnormalities, including atheromatous changes with calcification in the root of the aorta and aortic valve, along with numerous collateral vessels originating from the left main coronary artery. Additionally, cystic nodules containing cysticercus larvae were identified within the myocardium, suggesting cardiac cysticercosis. The cause of death was determined to be complications related to the snakebite. This case emphasizes the importance of considering multiple potential etiologies in complex clinical presentations, especially in the tropics.

6.
Article in English | MEDLINE | ID: mdl-38764317

ABSTRACT

BACKGROUND: Data using real-world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real-world patients with documented AR. METHODS: Using a deidentified data set (January 2018-March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all-cause mortality without AVR were examined using Kaplan-Meier estimates and compared using the log-rank test. RESULTS: Within the data set, 845,113 patients had AR severity documented. For moderate-to-severe or severe AR, respectively, 2-year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%-45.3%] and 65.4% [63.3%-67.4%]) and AVR (19.4% [17.6%-21.1%] and 46.5% [44.2%-48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2-year mortality for untreated patients with left ventricular end-systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%-39.1%]) and severe (37.2% [24.9%-47.5%]) AR. CONCLUSIONS: Moderate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.

7.
Article in English | MEDLINE | ID: mdl-38738913

ABSTRACT

OBJECTIVE: Few studies have examined the impact of preoperative and surgical factors on the change in cosmetic survey scores after nasal Mohs reconstruction using a subset of the 10-item Standardized Cosmesis and Health Nasal Outcomes Survey-Cosmesis (SCHNOS-C). We aim to determine preoperative and surgical factors that impact cosmetic outcomes following Mohs nasal reconstruction. STUDY DESIGN: Retrospective analysis. SETTING: Nasal Mohs reconstruction patients at a tertiary medical center. METHODS: All patients receiving Mohs reconstruction of any nasal subunit at a tertiary medical center were analyzed. Variables collected included demographic and Mohs defect/reconstruction characteristics. Primary outcomes were changes in cosmetic (SCHNOS-C) scores and revision rates. Multivariable analysis was used to identify independent predictors of cosmetic scores/revision. RESULTS: We included 296 patients for analysis. On multivariable logistic regression, factors contributing to better final cosmetic scores were receiving a skin/composite graft (odds ratio [OR]: 0.22, 95% confidence interval: 0.06-0.68, P = .014) compared to a local flaps. Women were more likely to have worsening cosmetic scores (OR: 2.27, 1.06-4.99, P = .037). Only initial cosmetic scores independently predicted receiving any revision (OR: 1.11, 1.03-1.20, P = .006). CONCLUSION: Average SCHNOS-C scores after nasal reconstruction of Mohs defects are low. Only worse patient reported SCHNOS-C scores predicted revision. It is important to understand preoperative and surgical factors that affect cosmetic outcomes to optimize patient counseling and reconstructive planning. Patient perception is a key factor in predicting revisions.

8.
Cell Rep ; 43(5): 114175, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38691456

ABSTRACT

Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.


Subject(s)
Neoplasms , Transcription Factors , Humans , Transcription Factors/metabolism , Transcription Factors/genetics , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Cell Line, Tumor , TEA Domain Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Cell Proliferation
9.
bioRxiv ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38617348

ABSTRACT

This study introduces the GeneTerrain Knowledge Map Representation (GTKM), a novel method for visualizing gene expression data in cancer research. GTKM leverages protein-protein interactions to graphically display differentially expressed genes (DEGs) on a 2-dimensional contour plot, offering a more nuanced understanding of gene interactions and expression patterns compared to traditional heatmap methods. The research demonstrates GTKM's utility through four case studies on glioblastoma (GBM) datasets, focusing on survival analysis, subtype identification, IDH1 mutation analysis, and drug sensitivities of different tumor cell lines. Additionally, a prototype website has been developed to showcase these findings, indicating the method's adaptability for various cancer types. The study reveals that GTKM effectively identifies gene patterns associated with different clinical outcomes in GBM, and its profiles enable the identification of sub-gene signature patterns crucial for predicting survival. The methodology promises significant advancements in precision medicine, providing a powerful tool for understanding complex gene interactions and identifying potential therapeutic targets in cancer treatment.

10.
Cureus ; 16(3): e55797, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38586618

ABSTRACT

The artery of Percheron (AOP) is a unique variant of the thalamic and midbrain perforating arteries. It originates from the P1 branch of the posterior cerebral artery (PCA) and supplies the bilateral paramedian thalami (BPT) along with variable contributions to the rostral midbrain. Four infarction patterns have been identified as a result of an AOP stroke, each associated with varying prognostic outcomes. We present an 89-year-old female with an AOP infarction and discuss the associated symptoms, implicated anatomy, and prognosis.

11.
Article in English | MEDLINE | ID: mdl-38667749

ABSTRACT

OBJECTIVE: There is a trend towards nonintensive care unit (ICU) or specialty ward management of select patients. Here, we examine postoperative outcomes for patients transferred to a general ward following microvascular free flap (FF) reconstruction of the head and neck. STUDY DESIGN: Retrospective quality control study. SETTING: Single tertiary care center. METHODS: Consecutive patients who underwent FF of the head and neck before and after a change in protocol from immediate postoperative monitoring in the ICU ("Pre-protocol") to the general ward setting ("Post-protocol"). Outcomes included overall length of stay (LOS), ICU LOS, FF compromise, and postoperative complications. RESULTS: A total of 150 patients were included, 70 in the pre-protocol group and 80 in the post-protocol group. There were no significant differences in age, sex, comorbidities, tumor stage, or type of FF. Mean LOS decreased from 8.18 to 7.68 days (P = .4), and mean ICU LOS decreased significantly from 5.2 to 1.7 days (P < .01). There were no significant differences in postoperative or airway-related complications (P = .6) or FF failure rate (2.9% vs 2.6%, P > .9). There was a non-significant increase in ancillary consults in the post-protocol group (45% vs 33%, P = .13) and a significant increase in rapid response team calls, a nurse-driven safety net for abnormal vitals or mental status (19% vs 3%, P = .003). CONCLUSION: We show the successful implementation of a protocol shifting care of FF patients from the ICU to a general ward postoperatively, suggesting management on the floor with less frequent flap monitoring is safe and conserves ICU beds. Additional teaching and familiarity with these patients may over time reduce the rapid response calls.

12.
Eur Heart J Case Rep ; 8(4): ytae192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38665427

ABSTRACT

Background: Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital abnormality that may be encountered during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Case summary: A 65-year-old man presented with chest pain and signs of heart failure. Electrocardiogram demonstrated atrial fibrillation with ST elevation in the high lateral leads, and he was taken emergently to the cardiac catheterization laboratory for primary PCI. Coronary angiography identified the culprit to be an occluded anomalous left main coronary artery (LMCA) arising from the right coronary cusp, and primary PCI was successfully performed in the LMCA and the left anterior descending artery (LAD). Computed tomography angiography confirmed a benign retroaortic course of the anomalous LMCA with no additional high-risk features, as well as a new left atrial appendage thrombus. He subsequently developed deep venous thrombosis, acute pulmonary embolism, and acute kidney injury secondary to renal artery embolism with associated infarction. Workup for patent foramen ovale and thrombophilia were negative, and he was discharged in a stable condition. At 2-month follow-up, he was asymptomatic with no evidence of myocardial ischaemia on stress cardiac magnetic resonance imaging. Discussion: We present the first reported case of an occluded anomalous LMCA arising from the right coronary sinus in a patient presenting with STEMI. Rapid recognition of this congenital anomaly and selection of an appropriate guide catheter were keys to achieving timely reperfusion and a good outcome in this case.

13.
J Biomol Struct Dyn ; : 1-16, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682862

ABSTRACT

In lysozyme amyloidosis, fibrillar aggregates of lysozyme are associated with severe renal, hepatic, and gastrointestinal manifestations, with no definite therapy. Current drugs are now being tested in amyloidosis clinical trials as aggregation inhibitors to mitigate disease progression. The tetracycline group among antimicrobials in use is in phase II of clinical trials, whereas some macrolides and cephalosporins have shown neuroprotection. In the present study, two cephalosporins, ceftazidime (CZD) and cefotaxime (CXM), and a glycopeptide, vancomycin (VNC), are evaluated for inhibition of amyloid aggregation of hen egg white lysozyme (HEWL) under two conditions (i) 4 M guanidine hydrochloride (GuHCl) at pH 6.5 and 37° C, (ii) At pH 1.5 and 65 °C. Fluorescence quench titration and molecular docking methods report that CZD, CXM, and VNC interact more strongly with the partially folded intermediates (PFI) in comparison to the protein's natural state (N). However, only CZD and CXM proficiently inhibit the aggregation. Transmission electron microscopy, tinctorial assessments, and aggregation kinetics all support oligomer-level inhibition. Transition structures in CZD-HEWL and CXM-HEWL aggregation are shown by circular dichroism (CD). On the other hand, kinetic variables and soluble fraction assays point to a localized association of monomers. Intrinsic fluorescence (IF),1-Anilino 8-naphthalene sulphonic acid, and CD demonstrate structural and conformational modifications redesigning the PFI. GuHCl-induced unfolding and differential scanning fluorimetry suggested that the PFI monomers bound to CZD and CXM exhibited partial stability. Our results present two mechanisms that function in both solution conditions, creating a novel avenue for the screening of putative inhibitors for drug repurposing. We extend our proposed mechanisms in the designing of physical inhibitors of amyloid aggregation considering shorter time frames and foolproof methods.Communicated by Ramaswamy H. Sarma.


Drug repurposing has overcome failures in drug discovery and has reduced the overall time and cost of drug discovery and development.We examined the effect of screened antibiotics, ceftazidime (CZD), cefotaxime (CXM), and vancomycin (VNC) on lysozyme aggregation under two solution conditions.These antibiotics inhibit/modulate the aggregation reactions by strongly interacting with aggregation-prone intermediate and modulation of conformation and stability.Our study puts forward with caution two cephalosporins for aggregation inhibition studies.

14.
Environ Sci Pollut Res Int ; 31(23): 33638-33650, 2024 May.
Article in English | MEDLINE | ID: mdl-38687453

ABSTRACT

The synthesis and characterization of chitosan encapsulated copper oxide nanocomposites (CuNPs) using plant extracts for the photocatalytic degradation of second-generation antibiotics, cefixime and cefuroxime, were investigated. The study revealed that the presence of diverse chemical components in the plant extract significantly influenced the size of the CuNPs, with transmission electron microscopy (TEM) showing spherical shapes and sizes ranging from 11-35 nm. The encapsulation process was confirmed by an increase in size for certain samples, indicating successful encapsulation. X-ray photoelectron spectroscopy (XPS) analysis further elucidated the chemical makeup, confirming the valency state of Cu2+ and the presence of Cu-O bonding, with no contaminants detected. Photocatalytic activity assessments demonstrated that the copper oxide nanocomposites exhibited significant degradation capabilities against both antibiotics under UV light irradiation, with encapsulated nanocomposites (EnCu30) showing up to 96.18% degradation of cefuroxime within 60 min. The study highlighted the influence of chitosan encapsulation on enhancing photocatalytic performance, attributed to its high adsorption capability. Recycling studies confirmed the sustainability of the Cu nanocomposites, maintaining over 89% degradation rate after five consecutive cycles. This research underscores the potential of green-synthesized CuNPs as efficient, stable photocatalysts for the degradation of harmful antibiotics, contributing to environmental sustainability and public health protection.


Subject(s)
Anti-Bacterial Agents , Chitosan , Copper , Nanocomposites , Water Pollutants, Chemical , Chitosan/chemistry , Nanocomposites/chemistry , Copper/chemistry , Anti-Bacterial Agents/chemistry , Water Pollutants, Chemical/chemistry , Cephalosporins/chemistry , Green Chemistry Technology
15.
iScience ; 27(3): 109127, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38455979

ABSTRACT

NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language texts, special characters in drug SMILES have specific meanings and cannot be ignored. We introduce a novel NLP-based method that extracts interpretable sequences and essential features from drug SMILES notation using N-grams. Our method compares these features to Morgan fingerprint bit-vectors using UMAP-based embedding, and we validate its effectiveness through two personalized drug screening (PSD) case studies. Our NLP-based features are sparse and, when combined with gene expressions and disease phenotype features, produce better ML models for PSD. This approach provides a new way to analyze drug molecule structures represented as SMILES notation, which can help accelerate drug discovery efforts. We have also made our method accessible through a Python library.

16.
Cureus ; 16(2): e54466, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38510880

ABSTRACT

INTRODUCTION: The pterion and asterion serve as crucial landmarks on the skull, representing the antero-lateral and postero-lateral fontanelles in neonates, respectively. In clinical practice, these points play a pivotal role in guiding the understanding of deeper structures and their relationships to the head's surface. The thin calvarium at these junctures is susceptible to fractures, and the underlying vessels are prone to tear, often leading to extradural hematoma formation, necessitating burr hole surgery for evacuation. MATERIAL AND METHODS: The study involved 40 human dry skulls in Indians (n= 27 male (10.8%), n= 13 female (5.2%)) of unknown age, evaluating morphometric characteristics of 80 pterions and asterions. Measurements were conducted using a digital caliper (SKADIOO±0.2mm/0.01") in millimeters on both sides of each skull. The investigation also included an examination of sutural patterns in Pterion and asterion. RESULTS: Three types of sutural patterns were identified in the pterion, the most common being the sphenoparietal variety (75% on the right, 70% on the left), followed by the epipteric variety, which was the second most common (11.3% on the right, 12.5% on the left), and then the frontotemporal type (1.3% on the right, 2.5% on the left). Two sutural patterns were observed in the asterion: type 1 (presence of sutural bone) in 17.9% of skulls and type 2 (absence of sutural bone) in 82.1%. CONCLUSION: The differences in pterion and asterion positions across various populations explored in previous studies motivated us to conduct this research in the Indian population. Our findings revealed that among Indians, the predominant pterion type is predominantly sphenoparietal, whereas type 2 is the most prevalent in asterion. Understanding the clinical significance of the pterion and asterion is crucial for healthcare professionals to ensure precise and safe surgical procedures, particularly for the effective treatment of head trauma patients.

17.
Indian J Surg Oncol ; 15(1): 136-144, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38511046

ABSTRACT

Calcifying aponeurotic fibroma (CAF) is a rare soft tissue tumor which falls under the WHO category of benign fibroblastic and myofibroblastic tumors. It typically occurs on the distal extremities (hands and foot) of children and adolescents. Other less common sites include wrists, ankles, trunk and rarely legs and arms. These tumors present as a painless soft tissue mass, arising in the subcutis, and are usually connected to tendons or aponeuroses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the radiological investigations of choice; however, histopathology remains the diagnostic modality of choice for the diagnosis of CAF. We present a rare case of a 17-year-old boy who presented with a gradually progressive mass lesion on the leg which was later diagnosed as calcifying aponeurotic fibroma on histopathology.

18.
Life Sci ; 345: 122584, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38527668

ABSTRACT

AIM: Sepsis is a life-threatening clinical syndrome comprising multiorgan dysfunctions caused by a disproportionate body immune response. There are several animal sepsis models which are based on cecum ligation, cecal puncture, and cecum slurry injection. The major limitation of all current sepsis models is the high variability owing to the variable degree of ligation, puncture and inconsistent microbial composition used for sepsis initiation. The primary objective of this work is to demonstrate the feasibility of a standardized method for sepsis development. MATERIALS AND METHODS: The cecal slurry bacterial culture was developed and preserved in glycerol stocks. Antibiotics aztreonam and vancomycin were used for generating several defined, enriched cecal slurry bacterial cultures. Mice survival was assessed until 48 hrs post injection, and the tissue samples were collected after 10 hrs from sepsis initiation. KEY FINDINGS: The results indicate that increasing polymicrobial load resulted in lower survival rates and was associated with the higher number of infiltrating immune cells and necrosis. H&E (haematoxylin & eosin) staining & serum markers revealed that septic mice exhibited increased inflammation and significant damage to the liver and kidneys. The defined Gram-negative and Gram-positive specific cecal slurry bacterial cultures were developed and their efficiency in inducing sepsis was characterized. SIGNIFICANCE: Enriched cecal slurry bacterial cultures can be stored in glycerol stocks at -80 °C. This has an ethical advantage of avoiding unnecessary animal euthanasia for each experiment and provides a standardization capability of sepsis development.


Subject(s)
Glycerol , Sepsis , Mice , Animals , Injections, Intraperitoneal , Sepsis/drug therapy , Inflammation/complications , Disease Models, Animal , Cecum , Ligation/adverse effects
19.
Int J Biol Macromol ; 264(Pt 1): 130614, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38447849

ABSTRACT

Mycobacterium tuberculosis (Mtb) caseinolytic protease B (ClpB) is a chaperone possessing a unique ability to resolubilize the aggregated proteins in vivo. ClpB has been shown to be important for the survival of Mtb within the host. Thus, it appears to be a promising target to develop new therapeutic molecules against tuberculosis. In this study, we have screened FDA approved compounds in silico to identify inhibitors against Mtb ClpB. In our screen, several compounds interacted with ClpB. The top four compounds, namely framycetin, gentamicin, ribostamycin and tobramycin showing the highest binding energy were selected for further investigation. MD simulations and tryptophan-based quenching of ClpB-drug complexes established that the selected inhibitors stably interacted with the target protein. The inhibitor and protein complexes were found to be stabilized by hydrogen bonding, and hydrophobic interactions. Although, the compounds did not affect the ATPase activity of ClpB significantly, the protein resolubilization activity of ClpB was remarkably reduced in their presence. All four compounds potently inhibited the growth of Mtb H37Ra. The antimycobacterial activity of the compounds appears to be due the inhibition of functional ClpB oligomer formation, in turn affecting its chaperonic activity.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Humans , Mycobacterium tuberculosis/metabolism , Molecular Chaperones/metabolism , Peptide Hydrolases
20.
Int J Biol Macromol ; 264(Pt 1): 130626, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38453123

ABSTRACT

Silver-Carrageenan (Ag/Carr) nanocomposite film for food packing application by the green method using Argemone albiflora leaf extract has been developed in this study. Different plant parts of Argemone albiflora (blue stem prickly poppy) are used all over the world for the treatment of microbial infections, jaundice, skin diseases etc. GC-MS analysis was used to examine the phytochemical found in the Argemone albiflora leaf extract which reduces the metal ions to nanoscale. The biopolymer employed in the synthesis of nanocomposite film was carrageenan, a natural carbohydrate (polysaccharide) extracted from edible red seaweeds. We developed a food packing that is biodegradable, eco-friendly, economical and free from harmful chemicals. These films possess better UV barrier and mechanical and antimicrobial properties with 1 mM AgNO3 solution. The presence of silver nanoparticles in the carrageenan matrix was evident from FESEM. The mechanical properties were analysed by a Universal testing machine (UTM) and different properties like water vapour permeability (WVP), moisture content (MC) and total soluble matter (TSM) important for food packing applications were also analysed. The antimicrobial properties of the synthesized film samples were studied against E. coli and S. aureus pathogenic bacteria. These films were employed for the storage of cottage cheese (dairy product) and strawberries (fruit). This packing increased the shelf life of the packed food effectively. Ag/Carr films are biodegradable within four weeks.


Subject(s)
Anti-Infective Agents , Argemone , Metal Nanoparticles , Nanocomposites , Carrageenan/chemistry , Silver/chemistry , Food Packaging , Metal Nanoparticles/chemistry , Escherichia coli , Staphylococcus aureus , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Nanocomposites/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
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