Infectious disorders drug targets最新文献

Introduction: Acute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population.

Methods: This study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for bio-chemical analysis, with subsequent data analysis conducted using statistical methods.

Results and discussion: The following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above.

Conclusion: Biochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients.

This review explores various biliary tract diseases caused by different organisms, in-cluding cholelithiasis, hepatolithiasis, and choledocholithiasis. The biliary tract's primary func-tions include collecting, storing, concentrating, and delivering bile juice produced by the liver. Neurohormonal systems involving the vagus and splanchnic nerves, alongside cholecystokinin, regulate gallbladder movement during fasting and digestion. Under normal conditions, bile acids play a crucial role, with approximately 95% being reabsorbed by the intestinal epithelium and returned to the liver via the portal vein system. The liver, often hailed as a miracle worker, de-toxifies, purifies, and regenerates, performing essential functions in the body. Recent research indicates that the gallbladder, akin to the intestine, harbors a diverse microbiota. Additionally, the biliary mucosa features chemical, mechanical, and immunological barriers that promote im-munological tolerance. Hepatotoxicity remains a significant global health concern and a leading cause of mortality. Providing clear and accurate information on liver toxicity is critical, especially in the context of medication safety and public health. By refining these elements, this review can effectively convey the complexity and importance of biliary tract diseases and liver function in health and disease contexts.

Background: The understanding of the antibiotic resistance status of environmental nonO1/nonO139 V. cholerae [NOVC] in relation to other illnesses, which can vary in severity from mild to life-threatening, is limited. However, it is important to note that NOVC-related infections are increasing and serve as a significant illustration of emerging human diseases associated with climate change. The primary objective of the present study was to assess the rates of resistance observed in environmental NOVC isolates across various years, and regions, and their resistance rates.

Methods: We performed a systematic search of Scopus, PubMed, Web of Science, and EMBASE databases [until May 2024] following PRISMA guidelines. All statistical analyses were carried out using the statistical package R.

Results: Our analysis included a total of 34 studies. According to the meta-regression, chlo-ramphenicol, rifampicin, ciprofloxacin, nalidixic acid, cotrimoxazole, kanamycin, trime-thoprim, amoxicillin/clavulanic acid, and tetracycline resistance rate increased over time. The lowest resistance rates were observed in Austria [amoxicillin; 0.6%], the United States [kana-mycin; 0.1% and tetracycline; 0.1%], Morocco [polymyxin B; 12%], and Spain [trimethoprim; 0.3%]. Conversely, the highest resistance rates were found in Spain [amoxicillin; 61%], Indo-nesia [kanamycin and tetracycline; 94.9%], India [polymyxin B; 97.8%], and Morocco [trime-thoprim; 48.9%].

Conclusion: The meta-analysis showed significant variability in antibiotic resistance patterns among environmental NOVC isolates across time and regions, emphasizing the need for tar-geted, time-specific, and country-specific approaches to address antibiotic resistance globally.

Background: Toxoplasmosis is a cosmopolitan infectious disease in warm-blooded 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 bioinfor-matics 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 prop-erties, secondary and tertiary structures, 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 con-tained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, eval-uation of antigenicity and allergenicity showed the protein to be an immunogen and non-aller-gen. 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 indicated that a stable loop was 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.

Background: SNP based association studies have revolutionized the field of biomed-icines. Enteric fever is a systemic disease with etiologic agents Salmonella enterica serovar typhi and paratyphi. It is a serious health issue worldwide and presents wide variations in incidence, rates, and severity. Previous investigations have revealed that genetic variations may lead to sus-ceptibility to typhoid fever. A current study was performed to investigate the potential association of PARK2_e01(-697) polymorphism with the susceptibility to typhoid in the Punjabi population.

Methods: For this case-control study, blood samples obtained from typhoid patients with positive Typhidot or blood culture test (n=72) and healthy controls (n=73) were processed for DNA ex-traction. The polymorphism PARK2_e01(-697) analysis was carried out by using PCR and RFLP.

Results: No allelic association was found between PARK2_e01(-697) and susceptibility to ty-phoid fever in the understudy population.

Conclusion: This case control study is the demonstration of the non-association of PARK2_e01(-697) with typhoid in the Pakistani population. Future research, using a larger population size, will help to elucidate the role of PARK2_e01(-697) polymorphism in typhoid pathogenesis.

Several comorbidities and illnesses have emerged after the COVID-19 pandemic and the introduction of vaccination based on a slightly modified SARS-CoV-2 spike protein. One of these diseases is epilepsy, where the dysfunctional RAS plays a crucial role in the propagation of the disorder. SARS-CoV-2 infects host cells by utilizing the angiotensin-converting enzyme Type 2 (ACE2) receptor, which allows the virus to infect various cell types, including those in the lungs, nasopharynx, kidneys, lymph nodes, small intestine, stomach, spleen, and brain, leading to widespread organ damage. Once SARS-CoV-2 binds to the ACE2 receptor, it can lead to the overactivation of the ACE/Ang II/AT1R axis. Consequently, higher levels of Ang II activate several deleterious pathways that promote inflammation, contributing to inflammatory responses in the body and exacerbating conditions such as seizures. Additionally, the excitatory effect of AT1R by Ang II excess due to ACE2 inhibition by SARS-CoV-2 or by the vaccine Spike protein may play a further role in the mechanism contributing to epilepsy.

Objective: The current study aimed to formulate and evaluate herbal gels con-taining essential oils for the treatment of infection caused by microbial species, i.e., S. au-reus, E. coli, P. aeruginosa, and B. subtilis. These species are also responsible for acne directly and indirectly.

Material and methods: The gels were prepared using a gelling agent with 1% Carbopol-940, and they were further evaluated for physical appearance, drug content, in-vitro drug release, viscosity, extrudability, pH, and spreadability. Further, anti-microbial screening was done with various microbial species.

Results: Studies revealed that the gel was highly effective against the selected species ex-cept for the fungal strain. ZOI was observed ranging from 3.1 ± 0.01 mm to 13.4 ± 0.14 mm. The maximum ZOI was observed at 13.4 ± 0.14 mm against S. aureus. The physical properties of the gel satisfied the standard parameters.

Conclusion: The prepared herbal gel was found to have highly promising activity against bacterial species associated with bacterial infection but in a dose-dependent manner. How-ever, more research is required.

Aims: The present study aimed to assess the antibacterial effect of co-loaded rutin and curcumin in mesoporous silica nanoparticles (Cur-Rut-MSNs).

Background: Rutin is a nontoxic phytochemical that is present expansively in vegetables and fruits. Curcumin is an active ingredient of Curcuma longa. Curcumin and rutin have a variety of therapeutic effects, essentially antimicrobial, anti-inflammatory, and antioxidant actions.

Objective: Low aqueous solubility and poor bioavailability of rutin and curcumin limit their application in therapeutic goals. One of the advantageous routes to improve their bioavailability and solubility is nanoformulation. Co-delivery of therapeutic agents has been reported to have better therapeutic effects than monotherapy.

Methods: The present study has evaluated the antibacterial properties of Cur-Rut-MSNs. The Minimum Inhibitory Concentration (MIC) of Cur-Rut-MSNs has been assessed against different bacteria.

Results: Cur-Rut-MSNs exerted significantly higher antibacterial effect than curcumin-loaded MSNs (Cur-MSNs) and rutin-loaded MSNs (Rut-MSNs) against Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis (p<0.05).

Conclusion: The antibacterial effect was enhanced by the co-loading of rutin and curcumin in MSNs. According to the findings of this study, Cur-Rut-MSNs exhibit an antibacterial effect and can be a favorable nanoformulation against planktonic bacteria.

Introduction: Cervical cancer is among the most common types of cancer in women and is associated with human papillomavirus (HPV) infection. The association between cervical cancer and high-risk HPV infection has been well documented. However, the effect of simultaneous infection with high- and low-risk HPV or low-risk HPV alone on the risk of developing cervical malignancy remains unanswered in guidelines.

Method: We investigated the association of high and low-risk HPVs (HR or LR) genotypes with cervical carcinoma risk and pathological and cytological information in cases recruited from a population-based cohort study of 790 patients. Correlation matrix and t-test were used for analysis.

Results: The percentage of HR+LR and HR-HPV16/18 were 9.30% and 11.20% in class II, 7.15% and 7.10% in class IV, and 7.15% and 5.80% in As-CUS smears. Interestingly, concurrent infection with HR-HPV and LR-HPV types led to a significant reduction in the risk of developing malignancy compared to the high-risk group (OR=0.3 (0.098-0.925), pvalue=0.04). The percentage of individuals with cervical malignancy was 10.2% and 28.2% within the co-infected and the HR-HPV participants.

Conclusion: Our findings suggest that simultaneous infection with high- and low-risk HPV may reduce the risk of cervical malignancy.