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1.
Article in English | MEDLINE | ID: mdl-38949300

ABSTRACT

BACKGROUND: Endoscopic approach has come up as a safe and feasible procedure for thyroidectomy with better cosmetic outcomes. However, concerns over its safety in terms of nerve injury and postoperative voice changes remain. This prospective study evaluated the role of vocal cord function assessment using laryngeal examination and voice analysis in patients who underwent endoscopic hemithyroidectomy either by the trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) or the bilateral axillobreast approach (BABA). METHODS: Thirty-nine consecutive patients were randomly allocated to either of the 2 groups of endoscopic hemithyroidectomy; 19 in TOETVA and 20 in the BABA groups. Vocal cord function was assessed subjectively using the GRBAS scale and objectively by acoustic analysis of parameters such as jitter, shimmer, mean frequency (F0), noise-to-harmonic ratio (NHR), and maximum phonatory time (MPT) at baseline, postoperative day 10, and 3 months after surgery. RESULTS: There were no significant differences in mean GRBAS scores and values of mean frequency, jitter and shimmer between the 2 groups and on postoperative day 10 and at 3 months compared with baseline. The mean NHR and MPT showed no differences between the 2 procedures. However, there was a significant decrease in their values on day 10 postsurgery, compared with baseline. These values returned to their baseline at 3 months. The other operative parameters were comparable between the 2 groups, except for the shorter mean operative time in the TOETVA group. CONCLUSIONS: Perioperative quantitative voice parameters were comparable with no statistically significant difference between the 2 techniques of endoscopic thyroidectomy.

2.
Cornea ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985894

ABSTRACT

PURPOSE: Positive vitreous pressure (PVP) secondary to intraoperative acute hypotony during penetrating keratoplasty can result in extrusion of the intraocular lens and vitreous. Currently described techniques are difficult or impossible to apply intraoperatively when positive vitreous pressure is noticed in an "open sky" situation after excision of the host corneal button. METHODS: We describe a technique where pupil scaffolding is used to prevent intraocular lens or crystalline lens extrusion by simply closing the pupil with a temporary suture that holds the retropupillary contents back. Once the eye is thus stabilized, the donor cornea is sutured rapidly after which the pupillary knot is cut and removed using microscissors and microforceps. RESULTS: Five patients undergoing penetrating keratoplasty under peribulbar anesthesia underwent this technique after experiencing PVP after host corneal button excision. PVP was successfully controlled in all 5 patients, and the optical grafts remained clear in the postoperative period. CONCLUSIONS: Temporary pupillary scaffolding can help control PVP and prevent ocular content extrusion during PKP surgeries.

3.
Small ; : e2403965, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994696

ABSTRACT

Nanotube and nanowire transistors hold great promises for future electronic and optoelectronic devices owing to their downscaling possibilities. In this work, a single multi-walled tungsten disulfide (WS2) nanotube is utilized as the channel of a back-gated field-effect transistor. The device exhibits a p-type behavior in ambient conditions, with a hole mobility µp ≈  1.4 cm2V-1s-1 and a subthreshold swing SS ≈ 10 V dec-1. Current-voltage characterization at different temperatures reveals that the device presents two slightly different asymmetric Schottky barriers at drain and source contacts. Self-powered photoconduction driven by the photovoltaic effect is demonstrated, and a photoresponsivity R ≈ 10 mAW-1 at 2 V drain bias and room temperature. Moreover, the transistor is tested for data storage applications. A two-state memory is reported, where positive and negative gate pulses drive the switching between two different current states, separated by a window of 130%. Finally, gate and light pulses are combined to demonstrate an optoelectronic memory with four well-separated states. The results herein presented are promising for data storage, Boolean logic, and neural network applications.

4.
Cureus ; 16(6): e62226, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39006631

ABSTRACT

Background and objectives Morphometric parameters such as radial inclination, palmar tilt, radial height, and ulnar variance exhibit considerable variations influenced by geographical, ethnic, racial, and individual factors. These parameters are pivotal in the context of distal radius fractures, distal radius plate design, and kinesiology. Understanding these variations is crucial for surgical precision and predicting complications. Methods This observational, retrospective study, conducted in a single hospital, aimed to determine the morphometric values of the distal end radius, specifically in the South Indian population. We analyzed 300 plain radiographs, encompassing 53.7% males and 46.3% females, with ages ranging from 17 to 89 years (mean age: 41.05 ± 15.8). Radial inclination, radial height, palmar tilt, and ulnar variance were measured on posteroanterior views, while palmar tilt was assessed on lateral wrist X-rays. Results In our study, significant gender-based and side-specific differences were observed. The mean length of the styloid process, palmar tilt, ulnar variance, anteroposterior diameter of the radius, transverse diameter of the radius, oblique width of the radius, and carpal height of the radius exhibited notable variations between males and females. Similarly, significant differences were noted between the right and left sides concerning ulnar variance and teardrop angle. Among males, a significant difference was observed only in the teardrop angle between the right and left sides (59.11 ± 7.25 vs. 62.01 ± 7.97). Conclusion The findings underscore the importance of recognizing local morphometric variations in the South Indian population. This knowledge not only enhances the ability to restore normal alignment post-distal radius fractures but also provides fundamental values for future research endeavors within the local demographic. The study acts as a foundational resource for advancing our understanding of the normal anatomy and variations in the distal radius, facilitating improved clinical outcomes and tailored surgical interventions.

5.
PeerJ Comput Sci ; 10: e2132, 2024.
Article in English | MEDLINE | ID: mdl-38983187

ABSTRACT

Wireless sensor networks (WSN) are among the most prominent current technologies. Its popularity has skyrocketed because of its capacity to operate in difficult situations. The WSN market encompasses various industries, including building automation, security networks, healthcare systems, logistics, and military operations. Therefore, increasing the energy efficiency of these networks is of utmost importance. Hierarchical topology, which typically uses a clustering methodology, is one of the most well-known methods for WSN energy optimization. To achieve energy efficiency in WSN, hierarchical topology low-energy adaptive clustering hierarchy (LEACH) was first introduced, and this served as the foundation. However, conventional LEACH has several limitations, which have led to extensive research into improving LEACH's efficacy in its current form. The use of particular algorithms and strategies to enhance the functionality of the conventional LEACH protocol forms the basis of ongoing efforts. Utilizing this enhanced LEACH, performance in terms of throughput and network life may be enhanced by concentrating on elements such as cluster head formation and transmission energy consumption. The enhanced LEACH algorithm demonstrates significant improvements in both throughput and network lifetime compared with conventional LEACH. Through rigorous experimentation, it was found that the enhanced algorithm increases the throughput by 25% on average, which is attributed to its dynamic clustering and optimized routing strategies. Furthermore, the network lifetime is extended by approximately 30%, primarily because of enhanced energy efficiency through adaptive clustering and transmission power control.

6.
Environ Res ; 259: 119528, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960355

ABSTRACT

BACKGROUND: While modeled estimates and studies in contaminated areas indicate high lead exposure among children in Bihar, India, local data on lead exposure in the child population is limited. OBJECTIVES: To characterize lead exposure, and assess potential sources of lead exposure among a state-representative sample of children and their pregnant mothers residing in Bihar. METHODS: Blood samples were collected from 697 children under five and 55 pregnant women from eight districts in Bihar. Blood lead levels were determined using capillary blood and a portable lead analyzer. Household demographics, home environment, behavior, and nutrition information were collected through computer-assisted personal interviews with primary caregivers. Logistic regression was used to assess associations between potential risk factors and elevated blood lead levels. RESULTS: More than 90% of children and 80% of pregnant women reported blood lead levels ≥5 µg/dL. Living near a lead-related industry and pica behavior of eating soil were significantly associated with increased odds of having elevated blood lead levels. Additional risk factors for having a blood level ≥5 µg/dL included the use of skin lightning cream (aOR = 5.11, 95%CI: 1.62, 16.16) and the use of eyeliners (aOR = 2.81, 95%CI: 1.14, 6.93). Having blood lead levels ≥10 µg/dL was also significantly associated with the household member who had an occupation or hobby involving the use of lead (aOR = 1.75, 95%CI: 1.13, 2.72). DISCUSSION: Elevated blood lead levels were prevalent among children and pregnant women in Bihar, indicating the urgent need for a comprehensive lead poisoning prevention strategy.

7.
Cureus ; 16(5): e60096, 2024 May.
Article in English | MEDLINE | ID: mdl-38860074

ABSTRACT

The presence of a supernumerary subserosal muscle layer of the bowel is an extremely unusual congenital development. The following is a report of diffuse involvement of the intestine with a supernumerary subserosal muscle coat. The current patient, a 29-year-old male, was evaluated in January 2022 for a long-standing history of subacute intestinal obstruction (SAIO). A preoperative CT scan of the abdomen and pelvis suggested mild dilatation and clumping of ileal loops in the right iliac fossa, with a subtle wall thickening of up to 5 mm. Intraoperatively, dense adhesions were noted between clumped bowel loops and the anterior abdominal wall. Following adhesiolysis, ileocecal resection with ileocolic anastomosis was done. The histopathological examination of the resected bowel segment showed irregular hypertrophy of circular and longitudinal muscle layers with the presence of an additional smooth muscle coat outer to the outer longitudinal layer that was seen in the ileum as well as the appendix. No evidence of vacuolar degeneration was noted, and ganglion cells were seen to be adequately present. The presence of additional smooth muscle bundles in the subserosa was confirmed with positive actin immunostaining. Additionally, CD117 staining was done that revealed a normal network of interstitial cells of Cajal. No evidence of active inflammation was noted in the resected bowel segment. Findings from the current case bring to light an extremely rare malformation of the muscularis propria of the intestine, namely a supernumerary subserosal muscle coat.

8.
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).

9.
Front Oncol ; 14: 1411539, 2024.
Article in English | MEDLINE | ID: mdl-38939334

ABSTRACT

Background: Pervasive transcription of the eukaryotic genome generates noncoding RNAs (ncRNAs), which regulate messenger RNA (mRNA) stability and translation. MicroRNAs (miRNAs/miRs) represent a group of well-studied ncRNAs that maintain cellular homeostasis. Thus, any aberration in miRNA expression can cause diseases, including carcinogenesis. According to microRNA microarray analyses, intronic miR-617 is significantly downregulated in oral squamous cell carcinoma (OSCC) tissues compared to normal oral tissues. Methods: The miR-617-mediated regulation of DDX27 is established by performing experiments on OSCC cell lines, patient samples, and xenograft nude mice model. Overexpression plasmid constructs, bisulphite sequencing PCR, bioinformatics analyses, RT-qPCR, Western blotting, dual-luciferase reporter assay, and cell-based assays are utilized to delineate the role of miR-617 in OSCC. Results: The present study shows that miR-617 has an anti-proliferative role in OSCC cells and is partly downregulated in OSCC cells due to the hypermethylation of its independent promoter. Further, we demonstrate that miR-617 upregulates DDX27 gene by interacting with its promoter in a dose-dependent and sequence-specific manner, and this interaction is found to be biologically relevant in OSCC patient samples. Subsequently, we show that miR-617 regulates cell proliferation, apoptosis, and anchorage-independent growth of OSCC cells by modulating DDX27 levels. Besides, our study shows that miR-617 exerts its effects through the PI3K/AKT/MTOR pathway via regulating DDX27 levels. Furthermore, the OSCC xenograft study in nude mice shows the anti-tumorigenic potential of miR-617. Conclusion: miR-617-mediated upregulation of DDX27 is a novel mechanism in OSCC and underscores the therapeutic potential of synthetic miR-617 mimics in cancer therapeutics. To the best of our knowledge, miR-617 is the 15th example of a miRNA that upregulates the expression of a protein-coding gene by interacting with its promoter.

10.
J Inorg Biochem ; 258: 112633, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38852292

ABSTRACT

The NO dioxygenation reaction catalyzed by heme-containing globin proteins is a crucial aerobic detoxification pathway. Accordingly, the second order reaction of NO with oxymyoglobin and oxyhemoglobin has been the focus of a large number of kinetic and spectroscopic studies. Stopped-flow and rapid-freeze-quench (RFQ) measurements have provided evidence for the formation of a Fe(III)-nitrato complex with millisecond lifetime prior to release of the nitrate product, but the temporal resolution of these techniques is insufficient for the characterization of precursor species. Most mechanistic models assume the formation of an initial Fe(III)-peroxynitrite species prior to homolytic cleavage of the OO bond and recombination of the resulting NO2 and Fe(IV)=O species. Here we report vibrational spectroscopy measurements for the reaction of oxymyoglobin with a photolabile caged NO donor at cryogenic temperatures. We show that this approach offers efficient formation and trapping of the Fe(III)-nitrato, enzyme-product, complex at 180 K. Resonance Raman spectra of the Fe(III)-nitrato complex trapped via RFQ in the liquid phase and photolabile NO release at cryogenic temperatures are indistinguishable, demonstrating the complementarity of these approaches. Caged NO is released by irradiation <180 K but diffusion into the heme pocket is fully inhibited. Our data provide no evidence for Fe(III)-peroxynitrite of Fe(IV)=O species, supporting low activation energies for the NO to nitrate conversion at the oxymyoglobin reaction site. Photorelease of NO at cryogenic temperatures allows monitoring of the reaction by transmittance FTIR which provides valuable quantitative information and promising prospects for the detection of protein sidechain reorganization events in NO-reacting metalloenzymes.


Subject(s)
Myoglobin , Nitric Oxide , Myoglobin/chemistry , Nitric Oxide/chemistry , Spectrum Analysis, Raman , Cold Temperature , Animals , Kinetics , Vibration
11.
J Extra Corpor Technol ; 56(2): 77-81, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888551

ABSTRACT

Venovenous bypass (VVB) is a technique used in liver transplantation (LT) to maintain hemodynamic stability and abdominal organ perfusion and thereby improve patient outcomes. Despite its perceived benefits, VVB utilization has declined globally due to concerns related to heparinization, major bleeding and the need for expertise. Recent advancements, such as percutaneous cannulation techniques and improved extracorporeal technology have improved the safety of VVB in LT. This paper presents a modified VVB circuit with enhanced safety features. Cannulation plays a pivotal role in VVB establishment, with percutaneous methods increasingly favored. Studies demonstrate VVB's efficacy in improving patient outcomes with lower incidence of acute kidney injury and reduced operative time and blood loss, with no added morbidity or mortality. However, its routine use faces challenges, with alternative techniques gaining traction. Our experience highlights VVB's role in various clinical scenarios, including patients with high Model for End-Stage Liver Disease (MELD) scores, challenging surgical anatomy, portal vein thrombosis and pre-existing cardiovascular disease, emphasizing its safety and efficacy. Continued research is needed to optimize VVB techniques and ensure better outcomes for liver transplant recipients.


Subject(s)
Liver Transplantation , Humans , Extracorporeal Circulation/methods , Liver Transplantation/methods , Treatment Outcome
12.
Asian Pac J Cancer Prev ; 25(6): 1935-1943, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38918654

ABSTRACT

OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.


Subject(s)
Curcumin , Head and Neck Neoplasms , Metformin , Neoplasms, Second Primary , Humans , Metformin/therapeutic use , Curcumin/therapeutic use , Head and Neck Neoplasms/prevention & control , Head and Neck Neoplasms/drug therapy , Double-Blind Method , Neoplasms, Second Primary/prevention & control , Male , Female , Squamous Cell Carcinoma of Head and Neck/prevention & control , Squamous Cell Carcinoma of Head and Neck/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Middle Aged , Adult , Follow-Up Studies , Prognosis , Research Design , Aged , Randomized Controlled Trials as Topic
13.
Article in English | MEDLINE | ID: mdl-38841992

ABSTRACT

PURPOSE OF REVIEW: The aim of this review article is to present current recommendations as well as knowledge gaps and controversies pertaining to commonly utilized postoperative pain management after solid organ transplantation in the abdominal cavity. RECENT FINDINGS: Postsurgical pain has been identified as one of the major challenges in recovery and treatment after solid organ transplants. Many perioperative interventions and management strategies are available for reducing and managing postoperative pain. Management should be tailored to the individual needs, taking an interdisciplinary and holistic approach and following enhanced recovery after surgery guidelines. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. SUMMARY: The optimal pain management regimen has not yet been definitively established, and current scientific evidence does not yet support the endorsement of a certain analgesic approach. This objective necessitates the need for high-quality randomized controlled trials.

14.
Org Biomol Chem ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38873754

ABSTRACT

Sonogashira coupling is a reaction of aryl/vinyl halides with terminal alkynes. It is used for the synthesis of conjugated enynes. Generally, copper (Cu) is required as a mediator for this reaction. It requires a long reaction time, high catalyst loading, or expensive ligands. Recently, homogeneous, heterogeneous, and nanocatalysts have been developed using organosulphur and organoselenium compounds as building blocks. Preformed complexes of metals with organosulphur and organoselenium ligands are used for homogeneous catalysis. Heterogeneous catalytic systems have also been developed using Cu, Pd, and Ni as metals. The nanocatalytic systems (synthesized using such ligands) include copper selenides and stabilized palladium(0) nanospecies. This article aims to cover the developments in the field of the processes and techniques used so far to generate catalytically relevant organic ligands having sulphur or selenium donor sites, the utility of such ligands in the syntheses of homogeneous, heterogeneous, and nanocatalytic systems, and critical analysis of their application in the catalysis of this coupling reaction. The results of catalysis are analyzed in terms of the effects of the S/Se donor, halogen atom of aryl halide, the effect of the presence/absence of electron-withdrawing or electron-donating groups or substituents on the aromatic ring of haloarenes/substituted phenylacetylenes, as well as the position (ortho or para) of the substitution. Substrate scope is discussed for all the kinds of catalysis. The supremacy of heterogeneous and nanocatalytic systems indicates promising future prospects.

15.
F1000Res ; 13: 110, 2024.
Article in English | MEDLINE | ID: mdl-38895702

ABSTRACT

Background: Researchers are focusing their emphasis on quick and real-time healthcare and monitoring systems because of the contemporary modern world's rapid technological improvements. One of the best options is smart healthcare, which uses a variety of on-body and off-body sensors and gadgets to monitor patients' health and exchange data with hospitals and healthcare professionals in real time. Utilizing the primary user (PU) spectrum, cognitive radio (CR) can be highly useful for efficient and intelligent healthcare systems to send and receive patient health data. Methods: In this work, we propose a method that combines energy detection (ED) and cyclostationary (CS) spectrum sensing (SS) algorithms. This method was used to test spectrum sensing in CR-based smart healthcare systems. The proposed ED-CS in cognitive radio systems improves the precision of the spectrum sensing. Owing to its straightforward implementation, ED is initially used to identify the idle spectrum. If the ED cannot find the idle spectrum, the signals are found using CS-SS, which uses the cyclic statistical properties of the signals to separate the main users from the interference. Results: In the simulation analysis, the probability of detection (Pd), probability of a false alarm (Pfa), power spectral density (PSD), and bit error rate (BER) of the proposed ED-CS is compared to those of the traditional Matched Filter (MF), ED, and CS. Conclusions: The results indicate that the suggested strategy improves the performance of the framework, making it more appropriate for smart healthcare applications.


Subject(s)
Algorithms , Delivery of Health Care , Humans , Spectrum Analysis/methods
16.
Article in English | MEDLINE | ID: mdl-38845282

ABSTRACT

BACKGROUND: The effect of standardizing an insertion and removal protocol for pVAD devices has not been previously described. OBJECTIVES: We sought to evaluate clinical outcomes in patients who underwent pVAD insertion pre- and post-protocol standardization. METHODS: All patients who underwent pVAD insertion that remained in place at index procedure completion between January 2017 and September 2023 at a single academic center for both high-risk PCI and cardiogenic shock indications were included in the study. The primary outcome was the incidence of limb ischemia and major bleeding before and after the protocol initiation. Secondary outcomes included in-hospital and 30-day MACCE rate (death, myocardial infarction, stroke, emergent CABG), and how often the operators followed the protocol. RESULTS: A total of 89 patients had pVAD left in place (29 pre-protocol initiation and 60 post-protocol initiation). There was a significant decrease in incidence of limb ischemia post-protocol initiation compared to pre (17.2 % vs 1.7 %, p = 0.01) but no difference in bleeding incidence (13.8 % vs 20.0 %, p = 0.47). Adherence increased in all components of the protocol except for right heart catheterization. CONCLUSION: Standardization of an insertion and removal protocol for pVAD devices led to a statistically significant decrease in limb ischemia in a high-risk patient population.

17.
J Org Chem ; 89(11): 7394-7407, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38754107

ABSTRACT

The biological and medicinal importance of indolocarbazoles has been known for the past several decades. However, in recent times, these compounds have been emerging as potential candidates for optoelectronic applications, although several challenges are associated with their synthesis. We report here a Pd(II)-catalyzed process for the synthesis of indolo[3,2-a]carbazoles. The reaction proceeded under neat conditions and in the presence of aqueous nonmetallic oxidant TBHP, and the products were purified directly after the completion of the reaction. Also, the possibility of employing the present method for reaction with gram-scale feed was investigated. A detailed single-crystal analysis of several indolo[3,2-a]carbazoles revealed how the molecular arrangement can be tuned by altering the functionalization. Finally, the developed molecules were screened computationally to assess their potential for possible use as hole transport materials (HTMs) for organic light-emitting diodes (OLEDs).

18.
J Clin Exp Hepatol ; 14(5): 101410, 2024.
Article in English | MEDLINE | ID: mdl-38716375

ABSTRACT

Background: Gallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC. Methods: Fresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting, respectively, in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 were analysed for predicting overall survival (OS), disease-free survival (DFS) and response to chemotherapy using Kaplan-Meier log-rank test and Cox regression multivariate analysis. Results: The mean age of the cohort was 50 ± 13.2 with 26 (48.1%) in patients having early stage gallbladder cancer (GBC). Over-expression of ABCB1 and ABCG2 was noted in 32/54 (59%) and 40/54 (74%) cases, respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases, respectively. The mean OS and DFS was 20.7 ± 11.5 and 19.3 ± 12.2 months at median follow-up of 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidences of late death and recurrence among over-expression and down-expression. Sub-group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC. Conclusion: Altered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC.

19.
PLoS One ; 19(5): e0296565, 2024.
Article in English | MEDLINE | ID: mdl-38781195

ABSTRACT

Epigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis. We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis. Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogene SRSF3 at the translational level only. The tumor-suppressive role of miR-6741-3p was established by various in vitro assays and in vivo study in NU/J athymic nude mice. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.


Subject(s)
Carcinoma, Squamous Cell , Gene Expression Regulation, Neoplastic , MicroRNAs , Mouth Neoplasms , Serine-Arginine Splicing Factors , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Animals , Cell Line, Tumor , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Mice , Gene Expression Regulation, Neoplastic/drug effects , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism , DNA Methylation , Introns/genetics , Mice, Nude , Azacitidine/pharmacology , Oncogenes/genetics
20.
Lab Anim Res ; 40(1): 22, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38773665

ABSTRACT

BACKGROUND: Toxicity by pesticide has become a global health issue and leaves a harmful impact on human health via various ways. The people exposed to pesticides in the rural population get affected by the harmful effects of it as they enter the human body system through skin, inhalation, oral administration, food chain and many more ways. The present work is designed to study the toxic effect of endosulfan in male (n=30) and female (n=30) Swiss albino mice. Endosulfan was administered by oral gavage (oral administration) method, at the dose of 3.5 mg/Kg body weight daily for period of 3 weeks, 5 weeks and 7 weeks. After the completion of the treatment, the mice were sacrificed and their ovary and testis tissues were dissected out to check the degeneration. The blood was collected for karyotyping, biochemical and hormonal analysis of pesticide induced genotoxicity. After 7 weeks of administration with Endosulfan, various abnormalities were observed in male and female mice. RESULTS: Treatment with endosulfan at the dose of 3.5 mg/Kg body weight caused a higher degree of degeneration in the reproductive organ of Swiss albino mice . Treatment by this pesticide generated degeneration in long duration of dosage for 3,5 and 7 weeks. Ovaries of endosulfan administered groups showed degenerated germinal epithelium, Graffian follicles and corpus luteum. In testis of endosulfan treated mice, microscopic examination showed that there is significant damage and reduction in the tissue of seminiferous tubules and primordial germ cells. High degree of degeneration caused the disarrangement and deformation of spermatogonia with the decrease in the number of Sertoli cells. Biochemical and hormonal properties was also affected by endosulfan treatment. There was significant 5 folds decrease in the testosterone value of endosulfan in 7 weeks treated mice in comparison to control (p < 0.0001) and similarly there was significant elevation in the estrogen levels found in 7th week endosulfan treated mice. It also influenced the level of free radicals as there was significant decrease (p < 0.0001) in the value in catalase levels in 7 weeks endosulfan treated male and female mice, while significant (p < 0.0001) increase in the values of lipid peroxidation levels as 8 folds and 10 folds in 7 weeks endosulfan treated male and female Swiss albino mice respectively. This study hence speculates that the endosulfan exposed population are at the risk of reproductive health hazards. CONCLUSIONS: The present study thus concludes that, endosulfan after 7 weeks of exposure caused significant reproductive damage to both male and female Swiss albino mice groups. Moreover, the karyotyping study also correlated the genotoxic damage in the mice.

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