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1.
Heliyon ; 10(12): e33049, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39021953

ABSTRACT

Seasonal influenza affects millions of lives worldwide, with the influenza A virus (IAV) responsible for pandemics and annual epidemics, causing the most severe illnesses resulting in patient hospitalizations or death. With IAV threatening the next global influenza pandemic, it is a race against time to search for antiviral drugs. Betacyanins are unique nitrogen-containing and water-soluble reddish-violet pigments that have been reported to possess antiviral properties against the dengue virus. This study aimed to examine the antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) on IAV-infected lung epithelial A549 cells. HPLC and LC-MS analysis of extracted betacyanin showed four betacyanins in the betacyanin fraction: phyllocactin, hylocerenin, betanin, and isobetanin. Cytotoxicity assay showed that betacyanin fractions were not cytotoxic to A549 cells at concentrations below 100 µg/mL. Betacyanin fraction concentrations of 12.5, 25.0, and 50.0 µg/mL prevented the formation of viral cytopathic effect and reduced virus titer in IAV-infected cells up to 72 h. A downregulation of protein and mRNA nucleoprotein expression levels was observed after treatment with 25.0 and 50.0 µg/mL of betacyanin fraction after 24 h, thereby providing evidence for the antiviral activity of betacyanin from red pitahaya against IAV in vitro.

2.
Clin Case Rep ; 12(7): e9172, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38993693

ABSTRACT

Key Clinical Message: Pituitary apoplexy is a medical and surgical emergency requiring prompt diagnosis and often urgent treatment to manage symptoms and prevent further complications. Abstract: This report describes the successful management of a 37-year-old pregnant woman with a history of pituitary macroadenoma and apoplexy during a twin pregnancy. Presenting with bitemporal vision loss, a common pituitary adenoma symptom, she showed no other alarming signs despite a twin pregnancy. Successful endoscopic resection improved her vision, and postoperative recovery was uneventful. The discussion underscores significance of the diagnostic utility of contrast MRI. The patient's favorable outcome supports endoscopic resection feasibility in pregnant individuals with pituitary apoplexy.

3.
Org Biomol Chem ; 22(28): 5809-5815, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38946460

ABSTRACT

The palladium-catalysed regioselective C-H chalcogenation of benzoxazines with disulfides and diselenides in air has been described. In this protocol, palladium acetate serves as the catalyst in conjunction with copper as an oxidizing agent. Through this approach, a wide array of sulfenylation and selenylation reactions of benzomorpholines have been effected, yielding results ranging from good to excellent. Thus, the established procedure demonstrates superb regioselectivity and a strong tolerance towards various functional groups and is suitable for gram-scale synthesis. Additionally, this synthetic approach offers a practical and convenient pathway for late-stage functionalization leading to the Rosenmund-von Braun reaction.

4.
Diagnostics (Basel) ; 14(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39001287

ABSTRACT

BACKGROUND: Audiological diagnosis and rehabilitation often involve the assessment of whether the maximum speech identification score (PBmax) is poorer than expected from the pure-tone average (PTA) threshold. This requires the estimation of the lower boundary of the PBmax values expected for a given PTA (one-tailed 95% confidence limit, CL). This study compares the accuracy and consistency of three methods for estimating the 95% CL. METHOD: The 95% CL values were estimated using a simulation method, the Harrell-Davis (HD) estimator, and non-linear quantile regression (nQR); the latter two are both distribution-free methods. The first two methods require the formation of sub-groups with different PTAs. Accuracy and consistency in the estimation of the 95% CL were assessed by applying each method to many random samples of 50% of the available data and using the fitted parameters to predict the data for the remaining 50%. STUDY SAMPLE: A total of 642 participants aged 17 to 84 years with sensorineural hearing loss were recruited from audiology clinics. Pure-tone audiograms were obtained and PBmax scores were measured using monosyllables at 40 dB above the speech recognition threshold or at the most comfortable level. RESULTS: For the simulation method, 6.7 to 8.2% of the PBmax values fell below the 95% CL for both ears, exceeding the target value of 5%. For the HD and nQR methods, the PBmax values fell below the estimated 95% CL for approximately 5% of the ears, indicating good accuracy. Consistency, estimated from the standard deviation of the deviations from the target value of 5%, was similar for all the methods. CONCLUSIONS: The nQR method is recommended because it has good accuracy and consistency, and it does not require the formation of arbitrary PTA sub-groups.

5.
Biochim Biophys Acta Rev Cancer ; 1879(5): 189157, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39032538

ABSTRACT

Mixed-lineage kinase 3 (MLK3) is a serine/threonine kinase of the MAPK Kinase kinase (MAP3K) family that plays critical roles in various biological processes, including cancer. Upon activation, MLK3 differentially activates downstream MAPKs, such as JNK, p38, and ERK. In addition, it regulates various non-canonical signaling pathways, such as ß-catenin, AMPK, Pin1, and PAK1, to regulate cell proliferation, apoptosis, invasion, and metastasis. Recent studies have also uncovered other potentially diverse roles of MLK3 in malignancy, which include metabolic reprogramming, cancer-associated inflammation, and evasion of cancer-related immune surveillance. The role of MLK3 in cancer is complex and cancer-specific, and an understanding of its function at the molecular level aligned specifically with the cancer hallmarks will have profound therapeutic implications for diagnosing and treating MLK3-dependent cancers. This review summarizes the current knowledge about the effect of MLK3 on the hallmarks of cancer, providing insights into its potential as a promising anticancer drug target.

6.
BMJ Case Rep ; 17(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960427

ABSTRACT

Factor X (FX) is a vitamin K-dependent enzyme, which acts as an important coagulation factor of coagulation cascade. FX deficiency is an autosomal recessive inherited disease and is often demonstrated in families with consanguity. Pregnancy in women with congenital FX deficiency has been associated with adverse fetal outcomes. We report a case of pregnancy in women with FX deficiency. The patient needed an immediate caesarean section at 38 weeks of gestation because of severe oligohydramnios and fetal distress. FX deficiency during pregnancy was effectively managed, leading to a positive outcome through the optimal utilisation of available resources.


Subject(s)
Cesarean Section , Factor X Deficiency , Humans , Female , Pregnancy , Factor X Deficiency/diagnosis , Factor X Deficiency/complications , Adult , Oligohydramnios , Pregnancy Complications, Hematologic/diagnosis , Pregnancy Outcome , Fetal Distress/etiology
7.
Cureus ; 16(6): e62661, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39036242

ABSTRACT

Background Bone marrow examination (BME) is an indispensable diagnostic tool to evaluate various hematological and non-hematological disorders. Bone marrow aspirate cytology and bone marrow trephine biopsy, even though performed simultaneously, are assessed at different points in time due to different processing methods. Aims and objective This study aims to assess and compare the role of bone marrow aspiration and trephine biopsy to formulate an effective and rapid method for diagnosing a wide spectrum of various hematological and non-hematological disorders. Materials and methods The approach of our study was a hospital-based prospective study conducted on 200 patients over a period of 1 year. The role of bone marrow aspiration and a trephine biopsy is to formulate an effective and rapid method for diagnosing a wide spectrum of hematological and non-hematological disorders. Results In our study, a total of 200 cases were studied, of whom 119 patients were male and 81 were female. The most common finding was erythroid hyperplasia, comprising 40 (20%) cases, followed by hypoplastic marrow, comprising 28 (14%) cases. Subsequently, there were 19 (9.5%) cases of acute leukemia, while 15 (7.5%) cases of chronic myeloid leukemia (CML) in the chronic phase were found. In our study, bone marrow aspirate and bone marrow trephine biopsy were found to positively correlate in 137 (68.5%) of the cases. Conclusion Bone marrow aspiration alone is sufficient for the diagnosis of megaloblastic anemia and most of the hematological malignancies. Bone marrow trephine biopsy is more appropriate for the detection of disorders of focal marrow involvement such as lymphoproliferative disorders and staging of lymphomas, metastatic cancers, granulomatous lesions, and hypoplastic marrow. However, it is strongly recommended that both procedures should be done simultaneously to ensure maximum diagnostic accuracy.

8.
RSC Adv ; 14(30): 21915-21937, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38989245

ABSTRACT

Skin carcinoma is one of the most prevalent types of carcinomas. Due to high incidence of side effects in conventional therapies (radiotherapy and chemotherapy), photodynamic therapy (PDT) has gained huge attention as an alternate treatment strategy. PDT involves the administration of photosensitizers (PS) to carcinoma cells which produce reactive oxygen species (ROS) on irradiation by specific wavelengths of light that result in cancer cells' death via apoptosis, autophagy, or necrosis. Topical delivery of PS to the skin cancer cells at the required concentration is a challenge due to the compounds' innate physicochemical characteristics. Nanocarriers have been observed to improve skin permeability and enhance the therapeutic efficiency of PDT. Polymeric nanoparticles (NPs), metallic NPs, and lipid nanocarriers have been reported to carry PS successfully with minimal side effects and high effectiveness in both melanoma and non-melanoma skin cancers. Advanced carriers such as quantum dots, microneedles, and cubosomes have also been addressed with reported studies to show their scope of use in PDT-assisted skin cancer treatment. In this review, nanocarrier-aided PDT in skin cancer therapies has been discussed with clinical trials and patents. Additionally, novel nanocarriers that are being investigated in PDT are also covered with their future prospects in skin carcinoma treatment.

9.
Eur Oral Res ; 58(2): 76-82, 2024 May 05.
Article in English | MEDLINE | ID: mdl-39011171

ABSTRACT

Purpose: The purpose of the study was to evaluate and compare the effect of beverages, denture cleanser and chlorhexidine gluconate solution on surface roughness of flexible denture base material. Materials and methods: Fifty flexible denture base resin specimens measuring 50±1mm in diameter and 0.5±0.05 mm in thickness were fabricated. The specimens were divided into five groups each containing ten specimens. The specimens were immersed in distilled water (Control group A); hot coffee (Group B); cold beverage (Group C); sodium perborate containing denture cleanser (Group D) and 2% chlorhexidine gluconate solution (Group E). The specimens were immersed for 10 min daily in mentioned solutions for up to 60 days. Surface roughness (Ra) was evaluated on the 1st, 20th and 60th day with the help of atomic force microscope. The statistical analysis was done using two-way ANOVA and Tukey's Post hoc test. Results: The two- way ANOVA revealed that the average Ra values varied significantly depending on the type of solution used for immersion (p<0.001) and the duration of immersion (p<0.001). Variation in surface roughness with cold beverage was highest (p=0.001). On the 60th day the surface roughness of flexible denture base resin material was higher with cold beverage (0.184 µm) and denture cleanser (0.203 µm) than that of distilled water (0.052 µm) hot coffee (0.030 µm) and 2% chlorhexidine gluconate (0.068 µm). Conclusion: Exposure to cold beverage, which was acidic in nature and peroxide containing denture cleanser, produces much rougher surface in the thermoplastic polyamide flexible denture base resin specimens.

10.
Prep Biochem Biotechnol ; : 1-9, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995969

ABSTRACT

Plant melanin, a natural pigment, has gained significant attention recently due to its potential therapeutic and industrial applications. In this study, melanin pigments were extracted from Nigerseed hulls (NH) via alkali and acid extraction methods, followed by acid hydrolysis, organic solvent treatment, and repeated precipitation. The solubility of NH melanin was assessed, revealing solubility in alkali and dimethyl sulfoxide (DMSO) but insolubility in other common organic solvents. High-performance liquid chromatography (HPLC) was employed to measure the purity of NH melanin in comparison to standard melanin, while elemental analysis indicated a similarity between melanin extracted from nigerseed hulls and the standard counterpart. LC-MS data revealed a molecular weight of NH melanin. Furthermore, the stability of melanin was evaluated under varying conditions including temperature, oxidants, reducing agents, light exposure, and metal ion presence. Results demonstrated significant effects of Mg2+, Cu2+, and Fe2+ metal ions on melanin stability, with a minor effect observed for Ca2+, while sodium hyposulfite was found to destabilize the pigments. Our findings suggest that nigerseed hulls hold promise as a novel source for efficient melanin production, with potential applications in the food sector, food packaging, and biomedical fields.

11.
ACS Infect Dis ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037752

ABSTRACT

Plasmodium sporozoites invade hepatocytes, transform into liver stages, and replicate into thousands of merozoites that infect erythrocytes and cause malaria. Proteins secreted from micronemes play an essential role in hepatocyte invasion, and unneeded micronemes are subsequently discarded for replication. The liver-stage parasites are potent immunogens that prevent malarial infection. Late liver stage-arresting genetically attenuated parasites (GAPs) exhibit greater protective efficacy than early GAP. However, the number of late liver-stage GAPs for generating GAPs with multiple gene deletions is limited. Here, we identified Scot1 (Sporozoite Conserved Orthologous Transcript 1), which was previously shown to be upregulated in sporozoites, and by endogenous tagging with mCherry, we demonstrated that it is expressed in the sporozoite and liver stages in micronemes. Using targeted gene deletion in Plasmodium berghei, we showed that Scot1 is essential for late liver-stage development. Scot1 KO sporozoites grew normally into liver stages but failed to initiate blood-stage infection in mice due to impaired apicoplast biogenesis and merozoite formation. Bioinformatic studies suggested that Scot1 is a metal-small-molecule carrier protein. Remarkably, supplementation with metals in the culture of infected Scot1 KO cells did not rescue their phenotype. Immunization with Scot1 KO sporozoites in C57BL/6 mice confers protection against malaria via infection. These proof-of-concept studies will enable the generation of P. falciparum Scot1 mutants that could be exploited to generate GAP malaria vaccines.

12.
Int Dent J ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39030097

ABSTRACT

INTRODUCTION AND AIMS: Root canal therapy is a crucial aspect of endodontic treatment aimed at preserving natural dentition. Over the years, advancements in three-dimensional (3D) technology have revolutionized diagnosis and treatment planning. Different 3D technologies are used in dental care, such as cone-beam computed tomography (CBCT), which ensures 3D slice visualization, root canal microanatomy, and dynamic navigation throughout the pulp cavity. By exploring the latest technological progress in this field, we seek to understand how these innovations are enhancing precision, efficiency, and patient outcomes, shedding light on the benefits and potential impact of 3D imaging in improving root canal procedures. METHODS: Literature was searched from different databases, including PubMed, ScienceDirect, The Cochrane Library, Scopus, and Google Scholar. Inclusion criteria involved studies on 3D technology in root canal therapy with comparison groups, including RCTs and non-RCTs. Excluded studies lacked 3D imaging advancements, a control group, or were review articles or case studies. Quality assessment utilized QUIN for in vitro studies and ROBINS-I for non-RCTs to evaluate the studies' validity. RESULTS: According to the PRISMA guidelines, among 5015 initial articles, 16 were included. CBCT was the most used 3D imaging technique for root imaging followed by micro-computed tomography (MCT) and limited CBCT (LCBCT) imaging methods. 2D radiographs and 2D histological methods and clearing techniques were the most common comparative modalities. Overall, 3D imaging streamlined dental treatment as clinicians could visualize much clearer and higher-quality images. Different resolutions and voxel sizes were applied to improve imaging quality. CONCLUSION: Three-dimensional imaging, especially CBCT, improves root canal treatments by providing superior image quality. CBCT outperforms other techniques like MCT and LCBCT, enhancing clarity. Varying resolutions and voxel sizes optimize the effectiveness of 3D imaging in root canal therapy. CLINICAL RELEVANCE: The advancements in 3D imaging technology, particularly CBCT, have significantly enhanced the diagnosis and treatment planning for root canal therapy. CBCT provides detailed insights into intricate root canal anatomy, improving diagnostic accuracy.

13.
PLoS One ; 19(7): e0292563, 2024.
Article in English | MEDLINE | ID: mdl-39052614

ABSTRACT

This study culturally adapted and validated a Nepalese version of the Abuse Assessment Screen (AAS) tool for identifying domestic violence among pregnant women in Nepal, creating the Nepalese Abuse Assessment Screen (N-AAS). International and national topic experts reviewed the initial N-AAS version using the Delphi method, and pregnant women participated in cognitive interviews, providing feedback on the N-AAS as user experts. Subsequent pre-testing of a comprehensive questionnaire, which included the translated version of the N-AAS, occurred in two tertiary care hospitals using an electronic format known as Color-Coded Audio Computer-Assisted Self-Interview (C-ACASI). The study assessed the content validity index, compared the concurrent validity of the N-AAS with the gold standard interview, estimated the prevalence of domestic violence from two hospitals, and calculated the Kappa coefficient. The reliability of the entire questionnaire was also evaluated through a test-retest analysis, with content validity rated as "good to excellent" by topic and user experts and high test-retest reliability (91.2-98.9%), indicating consistency across questionnaires completed at two different time points, with 12% of participants reporting any form of violence. The N-AAS demonstrated ≥91.7% specificity for all forms of abuse, accurately identifying non-abuse cases. In addition, moderate to excellent sensitivity was observed for emotional abuse (52.5%) and physical abuse since marriage (50%), while sensitivity for physical abuse in the past 12 months was 100%. Thus, the N-AAS demonstrated reliable test-retest results with a good Kappa coefficient and specificity, as well as showing excellent sensitivity for detecting recent physical abuse and moderate sensitivity for detecting emotional abuse and physical abuse since marriage. Because cultural context often leads women to normalize and tolerate abuse from spouses and family members and women are thus reluctant to report abuse, the results imply that the N-AAS can serve as a valuable screening tool for domestic abuse in antenatal care settings in Nepal.


Subject(s)
Domestic Violence , Humans , Female , Nepal/epidemiology , Pregnancy , Adult , Surveys and Questionnaires , Pregnant Women/psychology , Young Adult , Reproducibility of Results , Prevalence , Mass Screening/methods
14.
Int J Biol Macromol ; 275(Pt 1): 133586, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38960242

ABSTRACT

In the face of agricultural challenges posed by both abiotic and biotic stressors, phytopathogens emerge as formidable threats to crop productivity. Conventional methods, involving the use of pesticides and microbes, often lead to unintended consequences. In addressing this issue, ICAR -Indian Institute of Oilseeds Research (ICAR-IIOR) has developed a chitosan-based double-layer seed coating. Emphasizing crop input compatibility, entrapment, and characterization, the study has yielded promising results. The double-layer coating on groundnut seeds enhanced germination and seedling vigor. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) confirmed the structural changes and entrapment of crop inputs. The persistence of T. harzianum (Th4d) and Bradyrhizobium sp. in chitosan blended film in studied soils revealed that viable propogules of Th4d were recorded in double layer treatment combination with 3.54 and 3.50 Log CFUs/g of soil (colony forming units) and Bradyrhizobium sp. with 5.34 and 5.27 Log CFUs/g of soil at 90 days after application (DAA). Root colonization efficacy studies of Th4d and Bradyrhizobium sp. in groundnut crop in studied soils revealed that, maximum viable colonies were observed at 45 days after sowing (DAS). This comprehensive study highlights the potential of chitosan-based double-layer seed coating providing a promising and sustainable strategy for stress management in agriculture.

15.
Curr Cardiol Rev ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38963101

ABSTRACT

BACKGROUND: Brucellosis is a public health concern that affects multiple organs. However, cardiovascular problems arise infrequently, affecting fewer than 2% of cases, typically presenting as endocarditis. CASE PRESENTATION: A 50-year male was admitted with low-grade fever, night sweats, weight loss (13 kg), malaise, and generalized weakness for the past 6 months. On clinical examination, he was febrile with 39.0°C, an average heart rate of 54 bpm, and 100/40 mmHg blood pressure. On cardiovascular examination, S1 and S2 were soft with pan systolic murmur present in the mitral area, and the early diastolic murmur was present in the left third intercostal space. Electrocardiography was suggestive of third-degree heart block with AV dissociation. Transthoracic echocardiography showed mobile vegetations attached to multiple valves- an aortic valve (18.2x11.9mm) and a mitral valve (2.9x7.5mm) with perivalvular abscess. He was given oral doxycycline (100mg B.D.) and rifampicin (600mg/day); the patient responded, but the AV block did not resolve. CONCLUSION: This report has drawn attention to multivalvular involvement and cardiac rhythm abnormalities in Brucellosis (in this case, A.V. dissociation was present) because early diagnosis and treatment can cause a significant decrease in morbidity as well as mortality by appropriate treatment.

16.
Tuberculosis (Edinb) ; 148: 102536, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38976934

ABSTRACT

Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb.

17.
Photochem Photobiol ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38899585

ABSTRACT

Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various skin-related issues such as aging, allergies, and cancer. While several photo-protectants offer defense against ultraviolet radiation (UV-R), their effectiveness is often limited by photo-instability. Sunset Yellow (SY), an FDA-approved food dye, possesses significant UV-R and visible light absorption properties. However, its photoprotective potential has remained unexplored. Our investigation reveals that SY exhibits remarkable photostability for up to 8 h under both UV-R and sunlight. Notably, SY demonstrates the ability to quench ROS, including singlet oxygen (1O2), superoxide radicals ( O 2 · - $$ {\mathrm{O}}_2^{\cdotp -} $$ ), and hydroxyl radicals (·OH) induced by rose bengal, riboflavin and levofloxacin, respectively. Moreover, SY proves effective in protecting against the apoptotic and necrotic cell death induced by the phototoxicant chlorpromazine (CPZ) in HaCaT cells. Further, it was observed that SY imparts photoprotection by inhibiting intracellular ROS generation and calcium release. Genotoxicity evaluation provides additional evidence supporting SY's photoprotective effects against CPZ-induced DNA damage. In conclusion, these findings underscore the potential of SY as a promising photoprotective agent against the toxic hazards induced by phototoxicants, suggesting its prospective application in the formulation of broad-spectrum sunscreens.

18.
Front Genet ; 15: 1361610, 2024.
Article in English | MEDLINE | ID: mdl-38826807

ABSTRACT

Shigella dysenteriae has been recognized as the second most prevalent pathogen associated with diarrhea that contains blood, contributing to 12.9% of reported cases, and it is additionally responsible for approximately 200,000 deaths each year. Currently, there is no S. dysenteriae licensed vaccine. Multidrug resistance in all Shigella spp. is a growing concern. Current vaccines, such as O-polysaccharide (OPS) conjugates, are in clinical trials but are ineffective in children but protective in adults. Thus, innovative treatments and vaccines are needed to combat antibiotic resistance. In this study, we used immuno-informatics to design a new multiepitope vaccine and identified S. dysenteriae strain SD197's membrane protein targets using in-silico methods. The target protein was prioritized using membrane protein topology analysis to find membrane proteins. B and T-cell epitopes were predicted for vaccine formulation. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, a total of 8 B-cell epitopes, 12 MHC Class I epitopes, and 7 MHC Class II epitopes were identified for the Lipopolysaccharide export system permease protein LptF. Additionally, 17 MHC Class I epitopes and 14 MHC Class II epitopes were predicted for the Lipoprotein-releasing ABC transporter permease subunit LolE. These epitopes were selected and linked via KK, AAY, and GGGS linkers, respectively. To enhance the immunogenic response, RGD (arginine-glycine-aspartate) adjuvant was incorporated into the final vaccine construct. The refined vaccine structure exhibits a Ramachandran score of 91.5% and demonstrates stable interaction with TLR4. Normal Mode Analysis (NMA) reveals low eigenvalues (3.925996e-07), indicating steady and flexible molecular mobility of docked complexes. Codon optimization was carried out in an effective microbial expression system of the Escherichia coli K12 strain using the recombinant plasmid pET-28a (+). Finally, the entire in-silico analysis suggests that the suggested vaccine may induce a significant immune response against S. dysenteriae, making it a promising option for additional experimental trials.

19.
Cureus ; 16(5): e59508, 2024 May.
Article in English | MEDLINE | ID: mdl-38826983

ABSTRACT

Background Dyspepsia is one of the most common GI complaints encountered in clinical practice. Histopathological assessment of endoscopic gastric mucosa biopsy is crucial to delineate the exact cause of dyspepsia to guide patients' management. Objectives The aim of this study was to determine the histopathological spectrum of upper gastrointestinal (GI) tract endoscopic biopsies and to study the age and sex distribution of the predominant upper GI lesions. Methods A cross-sectional study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India, from January 2022 to December 2023. All endoscopic mucosal biopsies of the esophagus, stomach, and duodenum (first and second parts) lesions were examined under a microscope for histopathological findings. Results Out of 250 endoscopic biopsies studied, there were 76 cases of esophageal biopsies, 149 cases of gastric biopsies, and 25 cases of duodenal biopsies. The male-to-female ratio was 1.2:1. Non-neoplastic lesions were more common than neoplastic lesions. The most common lesions encountered were esophagitis in the esophagus, gastritis in the stomach, and duodenitis in the duodenum. Conclusion The main organic cause of dyspepsia in our setting was chronic gastritis. We conclude that endoscopy of the upper GI tract and histopathological examination help in the earlier detection of both benign and malignant lesions. This aids in better timely management of the patients and improves the overall treatment provided resulting in a better prognosis.

20.
J Cell Sci ; 137(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38832798

ABSTRACT

Plasmodium sporozoites are the infective forms of the malaria parasite in the mosquito and vertebrate host. Gliding motility allows sporozoites to migrate and invade mosquito salivary glands and mammalian hosts. Motility and invasion are powered by an actin-myosin motor complex linked to the glideosome, which contains glideosome-associated proteins (GAPs), MyoA and the myosin A tail-interacting protein (MTIP). However, the role of several proteins involved in gliding motility remains unknown. We identified that the S14 gene is upregulated in sporozoite from transcriptome data of Plasmodium yoelii and further confirmed its transcription in P. berghei sporozoites using real-time PCR. C-terminal 3×HA-mCherry tagging revealed that S14 is expressed and localized on the inner membrane complex of the sporozoites. We disrupted S14 in P. berghei and demonstrated that it is essential for sporozoite gliding motility, and salivary gland and hepatocyte invasion. The gliding and invasion-deficient S14 knockout sporozoites showed normal expression and organization of inner membrane complex and surface proteins. Taken together, our data show that S14 plays a role in the function of the glideosome and is essential for malaria transmission.


Subject(s)
Malaria , Plasmodium berghei , Protozoan Proteins , Sporozoites , Sporozoites/metabolism , Plasmodium berghei/metabolism , Plasmodium berghei/genetics , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Animals , Mice , Malaria/parasitology , Salivary Glands/parasitology , Salivary Glands/metabolism , Anopheles/parasitology
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