Infectious disorders drug targets最新文献

Introduction: Earlier reports described the possibility of higher SARS-CoV-2 infection and severity in patients with hematological malignancies. Given the importance and incidence of these malignancies, we aimed to systematically review SARS-CoV-2 infection and severity in patients with hematologic cancers.

Methods: We retrieved the relevant records by searching the keywords in online databases of PubMed, Web of Science, Cochrane, and Scopus on December 31st, 2021. A two-step screening; title/abstract and full-text screening, was employed to select the eligible studies. These eligible studies entered the final qualitative analysis. The study is adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of the results.

Results: Forty studies concerning different hematologic malignancies and the effect of COVID-19 infection on them were included in the final analysis. The findings showed that in general, the prevalence of SARS-CoV-2 infection and the severity of the disease are often higher in hematologic malignancies and the patients could experience higher morbidity and mortality compared to general populations.

Conclusion: It appeared that individuals with hematologic malignancies are more vulnerable to COVID-19 infection and they experience more severe disease with higher mortality rates. The presence of other comorbidities could also deteriorate this situation. Further investigation is recommended to evaluate the outcome of COVID-19 infection in different subtypes of hematologic malignancies.

Objective: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications.

Methods: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018.

Results: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6.

Conclusion: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future.

Background: Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for patients suspected to have coronavirus disease 2019 (COVID-19), which play a significant role in the diagnosis of COVID-19. However, the results of these studies are contradictory. The present study was conducted to evaluate biochemical, serological, and immunological tests for the diagnosis of COVID-19 patients.

Methods: This study was presented in accordance with the PRISMA protocol. This protocol is registered with the code CRD42019145410 in PROSPERO. We conducted a comprehensive literature search in databases, including Web of Science, PubMed/Medline, CINAHL Scopus, Cochrane Library, EMBASE, Science Direct, and EBSCO to find citations from the beginning of January 2019 until the beginning of April 2020 without any restrictions.

Results: Finally, 51 studies, including 5,490 COVID-19 patients, were included in the present metaanalysis. The prevalence of different factors observed in laboratory findings was as follows: the prevalence of lymphopenia in patients with COVID-19 accounted for 51.6% (95% CI: 44.0-59.1), elevated C-reactive protein (CRP) was 63.6% (95% CI: 57.0-69.8), elevated erythrocyte sedimentation rate (ESR) was 62.5% (95% CI: 50.1-73.5), elevated tumor necrosis factor alpha (TNFα) was 28.7% (95% CI: 9.0-62.1), elevated serum amyloid-A level was 74.7% (95% CI: 50.0-89.7), elevated procalcitonin level was 72.6% (95% CI: 58.1-83.5), elevated interleukin-6 level was 59.9% (95% CI: 48.2-70.5), reduced CD3 level was 68.3% (95% CI: 50.1-82.2), reduced CD4 level was 62.0% (95% CI: 51.1- 71.6), elevated lactate dehydrogenase (LDH) level accounted for 53.1% (95% CI: 43.6-62.4), elevated brain natriuretic peptide (BNP) accounted for 48.9% (95% CI: 30.4-67.7), reduced albumin and reduced pre-albumin levels in patients with COVID-19 were estimated to be 54.7% (95% CI: 38.1-70.2) and 49.0% (95% CI: 26.6-71.8), and D-dimer level was 44.9% (95% CI: 31.0-59.6).

Conclusion: The results show lymphopenia, elevated ESR level, elevated CRP level, elevated serum amyloid-A, elevated TNFα, elevated procalcitonin level, elevated interleukin-6 level, reduced CD3, reduced CD4, elevated BNP, elevated LDH, reduced albumin, reduced pre-albumin, and elevated Ddimer levels as the most common findings at the time of admission.

HFMD is an obvious disease in children mostly below the age of five constituting a public health challenge to Asian-Pacific and developing countries majorly. This disease is often caused by enterovirus 71 (EV71) and Coxsackievirus A16. HFMD is a mild degree fever and general illness which manifests for about 10 days. Young age, male gender, poor hygiene, and high social contacts are some risk factors. HFMD can be diagnosed clinically by isolating the virus from stool and pharynx and identifying it on Light microscopic examination. Polymerase Chain Reaction Assay is a gold standard for confirming the virus from swabbed lesions. Late confirmation could lead to severe complications. There are no specific treatments and vaccines licensed for general use in the treatment of various serotypes of HFMD. The major strategy to prevent and control this disease is to strictly follow the WHO 8 guidelines to curb the spread of the disease.

The elimination of leprosy has been possible with the available anti-leprotic drugs. However, the lepra reactions usually occur months or years after multi-drug therapy completion, and continue to be a formidable challenge mainly owing to its role in causing nerve damage and disability. Corticosteroids are commonly used but they lead to systemic complications, and hence require dose reduction and adjunct therapy with a different target. Various drugs with different targets have been identified and are in practice to treat lepra reactions. The newer targets can include genetic and tissue targets in the skin and nerve. Thalidomide treatment reducing pentraxin-3, toll-like receptor antagonists, minocycline, apremilast, immunomodulators, and tenidap can be helpful in lepra reaction. Other modalities to manage lepra reactions include plasma exchange, intravenous immunoglobulins, and immunotherapy. Most of these treatments are based only on the pathological process of the reaction and tend to be incomplete leading to recurrence. Newer multimodal approaches are required based on various biomarkers (genetic, tissue, serological), which can be monitored to prevent the recurrence of reactions. Hence, there is a need for newer targets and drugs to be identified for the management of lepra reactions.

Background: With an increasing trend of pathogenic bacteria developing resistance to the existing drugs, there is a need for newer therapeutic measures. Nigella sativa seeds and oil have been used for decades as Ayurveda, Unani Tibb and other forms of traditional medicine for various disorders. Thymoquinone is one of the active components of the N. sativa seeds.

Objective: The present study determines the antibacterial effect of crude methanolic extract N. sativa seeds and thymoquinone against bacteria causing wound infection.

Methods: Samples obtained from cases of wound infection received at a Microbiology laboratory attached to a tertiary care hospital over a period of six months were included in the study. The antibacterial effect of crude methanolic extract of N. sativa seeds was determined by the Punch Well method. The minimum inhibitory concentration (MIC) of thymoquinone against bacteria isolated from cases of wound infection was determined by the Micro Broth Dilution technique.

Results: A total of 60 isolates were collected from 60 samples of wound infection. By the Punch Well method, Staphylococcus aureus showed varying zones of inhibition whereas all gram-negative bacilli and Enterococcus faecalis did not show any zone of inhibition. Thymoquinone showed good antibacterial activity against S. aureus with MIC values ranging from 2-8μg/ml for most of the isolates. Uniformly, MIC of thymoquinone against all gram-negative bacilli and E. faecalis was >128μg/ml, p<0.001. It was found that methicillin-resistant S. aureus (MRSA) isolates showed higher MIC than methicillin sensitive S. aureus (MSSA) isolates p<0.05.

Conclusion: Antibacterial activity of thymoquinone was very good against S. aureus but showed limited activity against Enterobacteriaceae members and E. faecalis isolated from patients with wound infection. Thymoquinone may be considered a potential antibacterial agent against wound infection caused by S. aureus.

Background: Antimicrobial resistance among gram-negative bacteria has been growing, particularly in developing countries, like Iran. The emergence and spread of carbapenem-resistance mechanisms is a major public health concern because no definite treatments have yet been established for this problem. This study aimed to evaluate antibiotic susceptibility of gram-negative bacteria, metallo-β-lactamases (MBLs) and carbapenemase-producing genes, including bla _NDM, bla _VIM, and bla _IMP in patients referred to Children's Medical Center, Tehran, Iran.

Material and methods: In this cross-sectional study, a total of 944 gram-negative isolates were tested in the study, and antimicrobial susceptibility testing was performed. Moreover, MBL production of carbapenem-resistant isolates, as well as the presence of bla _NDM, bla _VIM, and bla _IMP, was investigated.

Results: The most common gram-negative isolated bacteria were Escherichia coli (489 samples, 52%), followed by Klebsiella pneumoniae (167 samples, 18%), Pseudomonas aeruginosa (101 samples, 11%), Enterobacter spp. (64 samples, 7%), Pseudomonas spp. (35 samples, 4%), Acinetobacter baumannii (18 samples, 2%), and Burkholderia cepacia (17 samples, 2%). Imipenemresistant was found in 75%, 61%, and 60% of Stenotrophomonas maltophilia, Enterobacter spp., and A. baumannii isolates, respectively. Moreover, the highest resistance to meropenem was observed in S. maltophilia, A. baumannii, P. aeruginosa, and B. cepacia (100%, 96%, 83%, and 61.5%, respectively). Double disk synergy test (DDST) results showed that 112 out of 255 carbapenem- resistant isolates (44%) were MBL-producing ones. The presence of the bla _NDM gene was identified in 32 (29%) of MBL-producing isolates, 13 of which were K. pneumoniae, 7 P. aeruginosa, and 7 E. coli, 3 Enterobacter spp., and 2 Klebsiella spp., respectively. The presence of the bla _IMP and bla _VIM genes was detected in 2 (2%) and 1 (1%) of MBL-producing isolates. These genes were detected in only MBL-producing P. aeruginosa isolates.

Conclusion: Our findings suggest the emergence of NDM-producing strains in our hospital, and bla NDM was the most frequently detected carbapenemase gene in MBL-producing P. aeruginosa, K. pneumoniae, and Klebsiella spp. Since such bacteria can easily spread among patients in the hospital, a strong infection control and prevention plan is highly recommended.

Purpose: The antimicrobial prescription in urinary tract infections (UTI) is driven by local data on its pathogenic spectrum and the resistance pattern exhibited by the disease-causing pathogens. We aimed to determine the bacteriological diversity of UTI causing pathogens and antimicrobial resistance in mostly gram-negative bacteria.

Methods: This retrospective hospital-based cross-sectional study analyzed the culture and sensitivity reports of urine samples from a referral centre in the Aljouf region of Saudi Arabia. All the antibiograms from January 1, 2020, to December 31st 2020, were included. The bacterial identification and antimicrobial testing were carried out by the BD Phoenix system (BD Diagnostics, Sparks, MD, USA). Antimicrobial testing was performed as per the Clinical and Laboratory Standard Institute recommendations. Frequencies of multidrug- and extensive drug resistance were calculated.

Results: Of the 1334 non-duplicate urine samples received, 422 (31.6%) bacterial growths were observed. Of these, 383 (90.8%) and 39 (9.2%) were gram-negative and gram-positive bacterial isolations, respectively. E. coli 161 (38.1%), K. pneumoniae 97 (23.0%), and E. faecalis 18 (4.3%) were frequent aetiologies of UTI. 309 (80.7%) of gram-negative bacteria were multidrug-resistant including 88 (23.0%) extensively drug-resistant. Overall, a resistance rate of > 55 % to 1st through 4th generation cephalosporins was observed except for cefoxitin (43.7%). A resistance rate of 37.6% was observed towards carbapenems, with the lowest rate (34.0%) to meropenem.

Conclusion: Multi-drug resistant gram-negative bacteria dominate the pathogenic spectrum of UTI in the region. A high resistance rate to cephalosporins and carbapenems exists in gram-negative organisms, causing UTI.