Infectious disorders drug targets最新文献

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.

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.

A mystery pathogen that has not yet infected the entire world's population is predicted to be the cause of Disease X, which will be contagious. According to WHO scientists, 50 million people are expected to die from Disease X, which would be 20 times deadlier than coronavirus disease 2019 (COVID-19). Many international initiatives are currently in motion to get ready for future pandemics. These include updating the International Health Regulation and the European Legislation, establishing the Health Emergency Preparedness and Response Authority (HERA), establishing international hubs, taking on the international challenge of developing a vaccine for Disease X within 100 days of recognition of emerging Pathogen X, and updating the prepared-ness plan of National Institute of Allergy and Infectious Diseases. Our current review's main objective is to determine whether black seeds (Nigella sativa) can manage Disease X. It has been established by several studies that black seeds (N. sativa) have antiviral, antibacterial, antimicro-bial, immunomodulatory, anti-inflammatory, and antioxidant properties, which would be useful in the management of Disease X. Black seeds (N. sativa) may be utilized in conjunction with supportive care and symptomatic therapy to manage Disease X in early phases. Future random-ized controlled clinical trials would further evaluate the safety and effectiveness of black seeds (N. sativa) in patients with Disease X.

Background: The alarming increase in antibiotic resistance urges alternative and efficacious antimicrobial solutions. Historically, medicinal plants have been used for therapeutic purposes, such as relieving pain and healing wounds. However, the evaluation of the natural therapeutic effects of medicinal plants in a manner that resembles how humans typically consume them is lacking. Therefore, in this study, many medicinal plants known to have some antimicrobial effects, including Frankincense, Garlic, Myrrh, and Ginger, were evaluated for their direct antibacterial activity in raw form.

Materials and methods: The direct antimicrobial activity of medicinal plants was evaluated against a variety of Gram-positive and Gram-negative bacterial strains, such as Staphylococcus aureus (S. Aureus), Acinetobacter baumannii and Klebsiella pneumoniae using agar well diffusion method and turbidity measurements in suspension culture.

Results: Out of all the tested medicinal plants, only raw garlic (Allium sativum) powder, when dissolved in water or vinegar, offered a straightforward antibacterial activity. A combination of garlic extract and vinegar increased antibacterial activity. Aqueous garlic extracts displayed robust antimicrobial activity against many resistant bacteria. Other medicinal plants used in this study had absent or minimal antibacterial effects.

Conclusion: Only garlic in its raw form was effective against antibiotic-resistant bacteria. The increase in the antibacterial activity of garlic when combined with vinegar suggests the synergistic activity of garlic. The straightforward antibacterial action of raw garlic may be strategically harnessed to combat the continuous challenge of increasing antibiotic resistance. This work promotes additional testing of more natural products (in raw form) and assesses their therapeutic effects clinically.

Background: Nasal colonization of Staphylococcus aureus increases the risk of nosocom-ial infections. Therefore, medications that can decolonize this pathogen can help prevent such infec-tions.

Objective: Our study aimed to compare the efficacy of povidone-iodine solution with intranasal mupi-rocin ointment in decolonizing S. aureus from the nasal cavity of healthcare workers.

Methods: This single-blinded randomized controlled trial was conducted on healthcare workers car-rying S. aureus nasally. After confirming nasal colonization through culture tests, participants were assigned to intervention groups A and B with an allocation ratio of 1:1. Group A received intranasal mupirocin ointment twice daily for five days, while group B received intranasal povidone-iodine so-lution twice daily for five days. After the decolonization period, samples were taken to compare the efficacy of both interventions in decolonizing S. aureus.

Results: In this study, 54 healthcare workers with a mean age of 39.37±7.80 years were included, 42.6% and 57.4% of whom were male and female, respectively. They were randomly assigned to each of the intervention groups. After the intervention, individuals who received povidone-iodine had significantly more positive cultures than those who received mupirocin (37.0% vs. 11.1%, P = 0.026). Additionally, factors such as age, gender, wards, and employment duration may affect the efficacy of mupirocin and povidone-iodine in decolonizing S. aureus from the nasal cavity.

Conclusion: The study findings revealed that both mupirocin and povidone-iodine were effective in decolonizing S. aureus from nasal carriers. However, mupirocin was more effective compared with povidone-iodine.

The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is one of the most challenging tasks in tuberculosis treatment. Conventional TB treatment regimens have proven ineffective in treating MDR-TB, thus demanding the development of new drugs followed by delivery systems. Bedaquiline, a novel anti-TB drug, has been reported to inhibit the ATP synthase required for the growth and replication of TB bacteria. Bedaquiline is able to target the persistent or latent form of TB, which remains difficult to treat with conventional drugs. This makes bedaquiline an important drug in the fight against MDR-TB. The drug has been approved by the US FDA as well as European Medicines Agency and is now widely used as part of combination therapy for the treatment of MDR-TB. Bedaquiline and its ad-vanced drug delivery system play a key role in tackling MDR-TB, providing a much-needed boost to control and eventually eliminate the disease. However, the cost of the drug remains a concern, and efforts are underway to make bedaquiline more accessible and affordable to patients in resource-limited settings. Nevertheless, the development of bedaquiline nanofor-mulations represents a significant step forward in the fight against TB and offers hope to millions of patients across the globe.