Infectious disorders drug targets最新文献

Introduction: Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis. It predominantly affects the lungs but can involve any organ in the body. Tracheo-oesophageal fistula (TEF) is one of the rare extrapulmonary manifestations of TB.

Case report: A 27-year-old male, otherwise healthy, reported to our outpatient department with complaints of fever, persistent cough, and significant weight loss. Subsequently, he was diagnosed with tuberculous tracheo-oesophageal fistula and pulmonary tuberculosis.

Discussion: The patient had an elevated ESR (52 mm) and underwent multiple imaging studies, including two normal barium swallow tests. Upper gastrointestinal endoscopy (UGIE) revealed two esophageal ulcers, one with a fistulous tract. Biopsy results suggested chronic esophagitis with granulomatous inflammation. Contrast-enhanced CT (CECT) of the thorax showed esophageal irregularities, air foci, and contrast extravasation into the bronchi, along with mediastinal lymphadenopathy and centrilobular nodules. Clinical and investigative findings suggested pulmonary tuberculosis with a tracheoesophageal fistula. The patient was discharged on a six-month antitubercular regimen with nutritional support via a nasogastric tube. Stent installation was planned if follow-up results were unfavorable.

Conclusion: Although tuberculosis is highly prevalent in India, TEF of tuberculous origin has been infrequently documented, particularly in young, healthy, immunocompetent individuals. The patient was successfully cured after initiating antitubercular therapy and subsequent follow-up.

Aim: This study was undertaken to compare the proteomic profile of sequential isolates of Beijing lineage Mycobacterium tuberculosis (M. tuberculosis). from a patient who developed drug-resistant tuberculosis (TB) in vivo during anti-tuberculosis therapy (ATT).

Background: Various studies have found the Beijing lineage of M. tuberculosis strongly associated with multidrug resistance (MDR) development.

Objectives: To identify and characterize the differentially expressed proteins during the in-vivo drug resistance conversion in M. tuberculosis Beijing lineage clinical isolates.

Methods: Drug-susceptible and drug-resistant M. tuberculosis isolates were confirmed as Beijing lineage. The isolates were grown in Middlebrook 7H9 medium for two weeks, and whole-cell lysate was prepared. Two-dimensional gel electrophoresis (2DGE) was used for proteomic analysis, and differentially expressed proteins were identified using MALDI-TOF-MS. Bioinformatics tools were used for molecular docking, phosphorylation, and pupylation site prediction.

Results: Seventeen proteins were found overexpressed in drug-resistant isolates as compared to drug-susceptible isolates, including the six proteins with unknown functions. Molecular docking showed that Isoniazid (INH) and rifampicin (RIF) interacted with their conserved domains/active sites of these proteins.

Discussion: We characterized two paired clinical isolates from a patient, one being INH and RIF susceptible and other resistant The comparative analysis of over expressed proteins showed that 5 of 17 proteins belonged to the cell wall and cell processes functional group, 3 to virulence, detoxifica-tion, adaptation functional group, and 3 to information pathways functional group, 2 proteins be-longed to insertion sequences and phage functional group, and 1 each (Rv0242c, Rv2970c and Rv3208A) to lipid metabolism, intermediary metabolism & respiration and regulatory functional group. We found that the Rv1827, Rv2626c, Rv2714, Rv2970c, Rv3208A, and Rv3881c proteins showed significant interaction in-silico with INH and RIF.

Conclusions: These over-expressed proteins probably play an important role in drug resistance de-velopment, and further studies on drug resistance mechanisms could provide more details. We also believe that these over-expressed proteins could be used as biomarkers for early prediction of in-vivo drug-resistance development.

Prostate-specific antigen (PSA) or gamma-selenoprotein or kallikrein-3 (KLK3) is a glycoprotein enzyme secreted by the epithelial cells of the prostate glands. It plays a crucial role in male fertility and is commonly used as a marker of prostate cancer. Antibodies to PSA anti-gen might play a role in male immune infertility. To date, the tests available in the market pro-vide information only about the presence or absence of these antibodies in body fluids, which is further confirmed by the Western blot test. There are no tests available to quantify the amount of anti-PSA antibodies in human body fluid. Hence, the present patent relates to in vitro immuno-assay for detecting and quantifying anti-prostate specific antigen (anti-PSA) antibodies in a hu-man body fluid sample. In particular, the immunoassay is an indirect ELISA. The assay has demonstrated high sensitivity and specificity, capable of detecting anti-PSA antibodies in body fluids within a range of 4.61 ng/mL to 431.37 ng/mL. To further validate the assay's specificity, additional experiments have been conducted using various samples, including chicken seminal fluid, and the serum and semen of azoospermic individuals. These samples, standardized to the same volume, have been incubated with a fixed amount of human PSA-coated antigen. Similar experiments have been performed with anti-human, anti-rabbit, anti-mouse, anti-horse, and anti-goat antibodies, further confirming the assay's specificity.

Background: Ongkea (Mezzetia parviflora Becc.) is a plant species employed as the traditional medicine by the Buton district people in Southeast Sulawesi, Indonesia. This traditional use suggests the plant's potential pharmacological activity, which may be associated with its endophytic fungi. Endophytic fungi, living symbiotically within plant tissues, are known to produce bioactive compounds that often mirror or enhance the host plant's therapeutic potential. In this study, we investigated the in vitro antioxidant activities of endophytic fungi, optimized the fermentation conditions for maximum production of bioactive metabolites, and compared the intracellular and extracellular antioxidant activities of the metabolites to gain a comprehensive understanding of their potential applications.

Methods: The related genera of endophytic fungi were determined by morphological and molecular analyses of the 18S rRNA gene. The antioxidant potential was assessed using methods involving DPPH free radical scavenging, hydrogen peroxide scavenging, and reducing power assays. Metabolite production was optimized by varying carbon and nitrogen sources.

Results: Based on the phylogenetic tree, the strain of endophytic fungi was assigned to Botryosphaeria sp. FUHM17, being closely related to Botryosphaeria sp. P483 KT213569. The most effective synthesis of antioxidant metabolites was demonstrated when glucose and yeast extract were employed as the respective carbon and nitrogen sources. The optimal production of antioxidant metabolites was observed when glucose and yeast extract were employed as a carbon source of 10 g/L glucose and a nitrogen source of 10 g/L yeast extract, respectively. Intracellular metabolites from selective fungi exhibited 26.67% DPPH scavenging activity after 10 days of culture. In addition, the intracellular and extracellular metabolite extracts had IC50 values of 208.07 μg/mL and 832.22 μg/mL, respectively. Compared to ascorbic acid (IC50: 5-10 μg/mL), the metabolites exhibited moderate antioxidant activity.

Conclusion: In the present study, the antioxidant metabolite of endophytic fungi was obtained from culture filtrate and biomass extract and confirmed by HPLC analysis. The findings indicated that the metabolites generated by endophytic fungi obtained from Ongkea hold promise as a prospective reservoir of unique natural antioxidants.

Enteric fever is a multi-systemic illness of major public health concern. Also known as typhoid fever, it is caused due to both Salmonella Typhi and Paratyphi species. Salmonella species have the ability to cause acute, latent, or chronic disease apart from biofilm formation. The outcome of infection depends on various factors, such as the growth state of Salmonella, the environmental conditions encountered at the time of infection, as well as the infected host, and the immune response elicited. If properly treated, many of the patients recover from the acute phase of enteric fever; however, only 3-5% of individuals can develop a chronic carrier state and can act as a reservoir of infection by continued shedding of bacteria in urine and faeces. In in-fected individuals, Salmonella colonizes the gall bladder and remains there long after symptoms subside, acting as a reservoir for the further spread of the disease. Symptomatic urinary tract in-fection (UTI) due to Salmonella is uncommon and is rarely encountered especially in an im-munocompromised patient with some underlying abnormality involving the urinary tract. In this review, we have tried to explore new directions in the field of Salmonella causing UTI in im-munocompetent patients, particularly as it relates to chronic infection.

Introduction: Epstein-Barr Virus (EBV) causes heterophile-positive Infectious Mononucleosis (IM), which manifests fever, sore throat, lymphadenopathy, and atypical lym-phocytosis. In the Central Nervous System (CNS), EBV can cause acute encephalitis, cere-bellar ataxia, Acute Disseminated Encephalomyelitis (ADEM), myelitis, meningitis, and radiculopathy. Reports of acute transverse myelitis linked to Epstein-Barr Virus (EBV) in-fection are limited; therefore, Longitudinally Extensive Transverse Myelitis (LETM) due to EBV infection is extremely uncommon.

Case report: An 18-year-old male, otherwise healthy, was admitted to the medicine depart-ment with ten days of fever, headache, and vomiting and five days of altered sensorium. Subsequently, his neurological test showed bilateral upper motor neuron quadriparesis, sen-sory impairment, and bladder-bowel involvement. Spinal T2W MRI indicated extensive cer-vical, thoracic, and lumbar hyperintense lesions. Laboratory investigations supported the di-agnosis, which revealed a positive IgM Antibody for EBV Viral Capsid Antigen (VCA) in serum and EBV DNA PCR in Cerebrospinal Fluid (CSF). The final diagnosis was EBV-induced acute meningoencephalitis with longitudinally extensive transverse myelitis and in-cidental aortic coarctation. Following methylprednisolone pulse therapy, the patient recov-ered significantly.

Conclusion: The present case report aims to share our experience by highlighting awareness of the rarity and treatment outcome of EBV-induced LETM.

Objective: The present study aimed to carry out the molecular identification of some bacteria in seminal fluid and investigation of their effects on semen quality Methods: The research cohort comprised 80 infertile individuals and 80 men with no fer-tility issues. Evaluation of sperm characteristics adhered to the protocols outlined by the World Health Organization. Detection and verification of pathogens were carried out by PCR.

Results: The prevalence of bacteriospermia in the semen of the infertile group exhibited a noticeable increase compared to the control group (p<0.05). The most abundant species in the semen of infertile men was Ureaplasma urealyticum (7.5%, p<0.05), followed by En-terococcus faecalis (6.25%, p>0.05). However, Streptococcus agalactiae was not found in any of the abnormal samples. In addition, we showed that Ureaplasma urealyticum signif-icantly affected the motility and morphology parameters. But, the presence of Enterococcus faecalis and Streptococcus agalactiae in semen samples of men does not lead to abnormal sperm production. Besides, there was no significant difference between the groups in terms of volume, but there was a significant difference in morphology, count, and total motility (p<0.001).

Conclusion: Bacteriospermia is linked to modifications in the characteristics of seminal fluid, potentially resulting in a reduction in the fertilization capacity of spermatozoa. Fur-thermore, Ureaplasma urealyticum is correlated with changes in semen properties that could contribute to a decrease in sperm fertilization potential.

Objective: This study aimed to assess the safety and efficacy of tissue Plasminogen Activator (tPA) in patients with COVID-19-induced severe Acute Respiratory Distress Syndrome (ARDS).

Methods: The intervention group consisted of eligible patients with severe ARDS due to COVID-19 admitted to the Intensive Care Unit (ICU) of a university hospital. We selected the control group from admitted patients treated in the same ICU within the same period. The intervention group received intravenous tPA as 10 mg stat, 40 mg over the first 2 hours, and 25-50 mg over the next 10 hours, followed by a therapeutic dose of enoxaparin. The control group only received the therapeutic dose of enoxaparin. The main outcomes were the rise of SpO2 within 24 hours of tPA administration, critical bleeding during tPA administration, 28-day in-hospital mortality following admission to the ICU, and length of stay in the ICU.

Results: We analyzed two sets of 15 patients in the intervention (mean age: 45 years, 69% male) and the control (mean age: 50 years, 50% male) groups. There was rapid relief of dyspnea and SpO2 rising within 24 hours in seven cases (45%) only in the intervention group with no significant organ-threatening bleeding. Death was observed in 5 of the tPA-treated patients (33.3%) versus 10 (66.7%) of the controls [adjusted OR (95%CI): 0.17 (0.03, 0.98), P value =0.068].

Conclusion: The administration of intravenous tPA as 10mg stat, 40 mg during 2 hours, and 50mg during the next 10 hours is safe, can cause a rapid relief of dyspnea, and be lifesaving.

Background: Toxoplasmosis is a cosmopolitan infectious disease in warmblooded mammals that poses a serious worldwide threat due to the lack of effective medications and vaccines.

Aims: The purpose of this study was to design a multi-epitope vaccine using several bioinformatics approaches against the antigens of Toxoplasma gondii (T. gondii).

Methods: Three proteins of T. gondii, including ROP18, MIC4, and SAG1 were analyzed to predict the most dominant B- and T-cell epitopes. Finally, we designed a chimeric immunogen RMS (ROP18, MIC4, and SAG1) using some domains of ROP18 (N377-E546), MIC4 (D302-G471), and SAG1 (T130-L299) linked by rigid linker A (EAAAK) A. Physicochemical properties, secondary and tertiary structure, antigenicity, and allergenicity of RMS were predicted utilizing immunoinformatic tools and servers.

Results: RMS protein had 545 amino acids with a molecular weight (MW) of 58,833.46 Da and a theoretical isoelectric point (IP) of 6.47. The secondary structure of RMS protein contained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, evaluation of antigenicity and allergenicity showed the protein to be an immunogen and nonallergen. The results of the Ramachandran plot indicated that 76.4%, 12.9%, and 10.7% of amino acid residues were incorporated in the favored, allowed, and outlier regions respectively. ΔG of the best-predicted mRNA secondary structure was -593.80 kcal/mol which indicates a stable loop is not formed at the 5' end.

Conclusion: Finally, the accuracy and precision of the in silico analysis must be confirmed by successful heterologous expression and experimental studies.