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Molecules (Basel, Switzerland) Nov 2021The purpose of this systematic review was to identify the available literature of production, purification, and characterization of proteases by endophytic fungi. There...
The purpose of this systematic review was to identify the available literature of production, purification, and characterization of proteases by endophytic fungi. There are few complete studies that entirely exhibit the production, characterization, and purification of proteases from endophytic fungi. This study followed the PRISMA, and the search was conducted on five databases: PubMed, PMC, Science Direct, Scopus Articles, and Web of Science up until 18 May 2021, with no time or language restrictions. The methodology of the selected studies was evaluated using GRADE. Protease production, optimization, purification, and characterization were the main evaluated outcomes. Of the 5540 initially gathered studies, 15 met the inclusion criteria after a two-step selection process. Only two studies optimized the protease production using statistical design and two reported enzyme purification and characterization. The genus and were the most cited among the eleven different genera of endophytic fungi evaluated in the selected articles. Six studies proved the ability of some endophytic fungi to produce fibrinolytic proteases, demonstrating that endophytic fungi can be exploited for the further production of agents used in thrombolytic therapy. However, further characterization and physicochemical studies are required to evaluate the real potential of endophytic fungi as sources of industrial enzymes.
Topics: Aspergillus; Endophytes; Fungal Proteins; Penicillium; Peptide Hydrolases
PubMed: 34834154
DOI: 10.3390/molecules26227062 -
Scientific Reports Nov 2021This study investigated whether C-reactive protein (CRP) can be used as a marker for the early detection and monitoring of malaria severity. Potentially relevant studies... (Meta-Analysis)
Meta-Analysis
This study investigated whether C-reactive protein (CRP) can be used as a marker for the early detection and monitoring of malaria severity. Potentially relevant studies were searched in Medline (PubMed), Scopus, and Web of Science. Differences in CRP between (1) severe malaria and uncomplicated malaria, (2) uncomplicated malaria and asymptomatic malaria, (3) uncomplicated malaria and febrile/healthy controls, and (4) asymptomatic malaria and febrile/healthy controls were estimated using random-effects models. Twenty-nine studies were included for meta-analysis. The results of meta-analysis demonstrated higher mean CRP levels in (1) patients with severe malaria compared with uncomplicated malaria (p < 0.001, standard mean difference [SMD]: 1.52, 95% confidence interval [CI]: 0.91-2.12, I: 95.1%), (2) patients with uncomplicated malaria than in those with asymptomatic malaria (p: 0.001, SMD: 1.65, 95% CI: 0.67-2.62, I: 96.7%), (3) patients with uncomplicated malaria compared with febrile/healthy controls (p < 0.001, SMD: 2.38, 95% CI: 1.37-3.40, I: 98.5%), and (4) patients with asymptomatic malaria compared with febrile/healthy controls (p < 0.001, SMD: 2.55, 95% CI: 1.60-3.50, I: 99.2%). This study demonstrated CRP levels are a biomarker for the early detection and monitoring of malaria severity.
Topics: Biomarkers; C-Reactive Protein; Early Diagnosis; Humans; Malaria; Plasmodium; Severity of Illness Index
PubMed: 34764364
DOI: 10.1038/s41598-021-01556-0 -
PLoS Neglected Tropical Diseases Nov 2021Vancomycin-resistant enterococci infection is a worrying worldwide clinical problem. To evaluate the accuracy of GeneXpert vanA/vanB in the diagnosis of VRE, we... (Meta-Analysis)
Meta-Analysis
PURPOSE
Vancomycin-resistant enterococci infection is a worrying worldwide clinical problem. To evaluate the accuracy of GeneXpert vanA/vanB in the diagnosis of VRE, we conducted a systematic review in the study.
METHODS
Experimental data were extracted from publications until May 03 2021 related to the diagnostic accuracy of GeneXpert vanA/vanB for VRE in PubMed, Embase, Web of Science and the Cochrane Library. The accuracy of GeneXpert vanA/vanB for VRE was evaluated using summary receiver to operate characteristic curve, pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio.
RESULTS
8 publications were divided into 3 groups according to two golden standard references, vanA and vanB group, vanA group, vanB group, including 6 researches, 5 researches and 5 researches, respectively. The pooled sensitivity and specificity of group vanA and vanB were 0.96 (95% CI, 0.93-0.98) and 0.90 (95% CI, 0.88-0.91) respectively. The DOR was 440.77 (95% CI, 37.92-5123.55). The pooled sensitivity and specificity of group vanA were 0.86 (95% CI, 0.81-0.90) and 0.99 (95% CI, 0.99-0.99) respectively, and those of group vanB were 0.85 (95% CI, 0.63-0.97) and 0.82 (95% CI, 0.80-0.83) respectively.
CONCLUSION
GeneXpert vanA/vanB can diagnose VRE with high-accuracy and shows greater accuracy in diagnosing vanA.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Gram-Positive Bacterial Infections; Humans; Sensitivity and Specificity; Vancomycin; Vancomycin-Resistant Enterococci
PubMed: 34748586
DOI: 10.1371/journal.pntd.0009869 -
Scientific Reports Nov 2021There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following... (Meta-Analysis)
Meta-Analysis
There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.
Topics: Antibodies, Monoclonal, Humanized; COVID-19; Humans; Odds Ratio; Receptors, Interleukin-6; Respiration, Artificial; SARS-CoV-2; Survival Rate; COVID-19 Drug Treatment
PubMed: 34728658
DOI: 10.1038/s41598-021-00726-4 -
International Journal of Molecular... Oct 2021The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past...
The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.
Topics: Antiviral Agents; COVID-19; Coronavirus 3C Proteases; Coronavirus Nucleocapsid Proteins; Flavonoids; Humans; Middle East Respiratory Syndrome Coronavirus; Phosphoproteins; Rhinovirus; SARS-CoV-2; Virus Internalization; COVID-19 Drug Treatment
PubMed: 34681727
DOI: 10.3390/ijms222011069 -
Artificial Organs Dec 2021Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies...
BACKGROUND
Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19.
METHODS
We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients.
RESULTS
We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment.
CONCLUSION
Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.
Topics: Adult; Aged; Biomarkers; COVID-19; Cytokines; Female; Hemoperfusion; Humans; Inflammation Mediators; Male; Middle Aged; Risk Factors; Treatment Outcome
PubMed: 34632596
DOI: 10.1111/aor.14078 -
Scientific Reports Oct 2021Kidney transplantation recipients (KTR) with coronavirus disease 2019 (COVID-19) are at higher risk of death than general population. However, mortality risk factors in... (Meta-Analysis)
Meta-Analysis
Kidney transplantation recipients (KTR) with coronavirus disease 2019 (COVID-19) are at higher risk of death than general population. However, mortality risk factors in KTR are still not clearly identified. Our objective was to systematically analyze published evidence for risk factors associated with mortality in COVID-19 KTR. Electronic databases were searched for eligible studies on 1 August 2021. All prospective and retrospective studies of COVID-19 in KTR were considered eligible without language restriction. Since data in case reports and series could potentially be subsets of larger studies, only studies with ≥ 50 patients were included. Random-effects model meta-analysis was used to calculate weighted mean difference (WMD) and pooled odds ratio (OR) of factors associated with mortality. From a total 1,137 articles retrieved, 13 were included in the systematic review and meta-analysis comprising 4,440 KTR. Compared with survivors, non-survivors were significantly older (WMD 10.5 years, 95% CI 9.3-11.8). KTR of deceased donor were at higher risk of death (OR 1.73, 95% CI 1.10-2.74). Comorbidities including diabetes mellitus, cardiovascular disease, and active cancer significantly increased mortality risk. KTR with dyspnea (OR 5.68, 95% CI 2.11-15.33) and pneumonia (OR 10.64, 95% CI 3.37-33.55) at presentation were at higher mortality risk, while diarrhea decreased the risk (OR 0.61, 95% CI 0.47-0.78). Acute kidney injury was associated with mortality (OR 3.24, 95% CI 1.36-7.70). Inflammatory markers were significantly higher in the non-survivors, including C-reactive protein, procalcitonin, and interleukine-6. A number of COVID-19 mortality risk factors were identified from KTR patient characteristics, presenting symptoms, and laboratory investigations. KTR with these risk factors should receive more intensive monitoring and early therapeutic interventions to optimize health outcomes.
Topics: Acute Kidney Injury; COVID-19; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Humans; Kidney Transplantation; Neoplasms; Risk Factors; SARS-CoV-2; Transplant Recipients
PubMed: 34625642
DOI: 10.1038/s41598-021-99713-y -
Journal of Neuroimmunology Nov 2021Background High efficacy disease modifying therapies (DMT) in the management of Multiple Sclerosis (MS) have a favorable effect on relapse rate and disability... (Meta-Analysis)
Meta-Analysis
Background High efficacy disease modifying therapies (DMT) in the management of Multiple Sclerosis (MS) have a favorable effect on relapse rate and disability progression; however, they can expose patients to significant risks, such as progressive multifocal leukoencephalopathy (PML). Objective The study aims to investigate prognostic factors that can determine outcome in MS-related PML patients. Methods We conducted a literature review and meta-analysis of 194 patients from 62 articles in PubMed, SCOPUS and EMBASE. Results Out of 194 patients (66.5% women, 33.5% men), 81% had progression in their EDSS score by at least 1 point from the time of PML diagnosis (EDSS-P group). The remaining patients had either stable or improved EDSS (EDSS-S group). In univariate analysis, older age at the time of PML diagnosis was associated with higher probability of disability accumulation and worsening of EDSS by at least 1 point (mean age = 44.8, p = 0.046). After adjusting for other variables, age at time of PML diagnosis remained a significant predictive variable in the multivariable logistic model (OR = 0.93, 95% CI: 0.88-0.99, p = 0.037). Natalizumab is the most commonly associated DMT linked to PML, followed by fingolimod and others including dimethyl fumarate, ocrelizumab, alemtuzumab. Among the different treatments used, no therapeutic agent was found to be superior in improving post-PML EDSS. Conclusions Younger age and lower JCV viral load at the time of PML diagnosis were associated with better outcome in MS-associate PML, while none of the PML therapies was superior over the others or associated with favorable outcome.
Topics: Age Factors; Antirheumatic Agents; Cerebrospinal Fluid; Disability Evaluation; Disease Progression; Endemic Diseases; Female; Humans; Immunocompromised Host; JC Virus; Leukoencephalopathy, Progressive Multifocal; Male; Multiple Sclerosis; Natalizumab; Prognosis; Severity of Illness Index; Viral Load
PubMed: 34547511
DOI: 10.1016/j.jneuroim.2021.577721 -
Acta Obstetricia Et Gynecologica... Dec 2021Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the...
INTRODUCTION
Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer.
MATERIAL AND METHODS
We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival.
RESULTS
We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%-100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival.
CONCLUSIONS
This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.
Topics: Alphapapillomavirus; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Disease-Free Survival; Female; Humans; Prognosis; Tumor Suppressor Protein p53; Vaginal Neoplasms
PubMed: 34546565
DOI: 10.1111/aogs.14260 -
Future Medicinal Chemistry Oct 2021The abundance, low cost, high density of functional groups and ease of purification of carbohydrates are among the most important features that make them a prime...
The abundance, low cost, high density of functional groups and ease of purification of carbohydrates are among the most important features that make them a prime candidate for designing therapeutics. Several carbohydrate-based molecules, of both natural and synthetic origin, are known for their wide range of therapeutic activities. The incorporation of a carbohydrate moiety not only retains the pharmacological characteristics of a molecule but also improves its activity. Several sugar conjugates have been designed and reported to inhibit acetylcholinesterase, β-amyloid and tau aggregation. This systematic review provides a brief overview of carbohydrate-based bioactive molecules having anti-Alzheimer's activity along with improved therapeutic potential. Most importantly, several reported carbohydrate-based molecules for Alzheimer's disease act on β-amyloid aggregation, tau protein, cholinesterase and oxidative stress, with enhanced pharmacokinetic and mechanistic properties. The prospect of designing carbohydrate-based molecules for Alzheimer's disease will definitely provide potential opportunities to discover novel carbohydrate-based drugs.
Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Butyrylcholinesterase; Carbohydrates; Cholinesterase Inhibitors; Humans; Molecular Structure; Neuroprotective Agents
PubMed: 34472382
DOI: 10.4155/fmc-2021-0109