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Frontiers in Genetics 2022Vegetable crops are known as protective foods due to their potential role in a balanced human diet, especially for vegetarians as they are a rich source of vitamins and...
Vegetable crops are known as protective foods due to their potential role in a balanced human diet, especially for vegetarians as they are a rich source of vitamins and minerals along with dietary fibers. Many biotic and abiotic stresses threaten the crop growth, yield and quality of these crops. These crops are annual, biennial and perennial in breeding behavior. Traditional breeding strategies pose many challenges in improving economic crop traits. As in most of the cases the large number of backcrosses and stringent selection pressure is required for the introgression of the useful traits into the germplasm, which is time and labour-intensive process. Plant scientists have improved economic traits like yield, quality, biotic stress resistance, abiotic stress tolerance, and improved nutritional quality of crops more precisely and accurately through the use of the revolutionary breeding method known as clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 (Cas9). The high mutation efficiency, less off-target consequences and simplicity of this technique has made it possible to attain novel germplasm resources through gene-directed mutation. It facilitates mutagenic response even in complicated genomes which are difficult to breed using traditional approaches. The revelation of functions of important genes with the advancement of whole-genome sequencing has facilitated the CRISPR-Cas9 editing to mutate the desired target genes. This technology speeds up the creation of new germplasm resources having better agro-economical traits. This review entails a detailed description of CRISPR-Cas9 gene editing technology along with its potential applications in olericulture, challenges faced and future prospects.
PubMed: 36482900
DOI: 10.3389/fgene.2022.1037091 -
Tropical Medicine & International... Jan 2023To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without... (Meta-Analysis)
Meta-Analysis Review
Direct evidence gap on fixed versus adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta-analysis.
OBJECTIVES
To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy.
METHODS
We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy.
RESULTS
Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (ROR ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The ROR for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses.
CONCLUSIONS
We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future.
REGISTRATION
The study protocol was registered in PROSPERO (CRD42019120905).
Topics: Adult; Humans; Evidence Gaps; Chagas Disease; Trypanosoma cruzi; Cardiomyopathies
PubMed: 36420767
DOI: 10.1111/tmi.13831 -
Cancer Immunology, Immunotherapy : CII Apr 2023T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy... (Meta-Analysis)
Meta-Analysis Review
Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor-engineered T cell (TCR-T) Therapy: a systematic review and meta-analysis.
BACKGROUND
T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy efficacy but is associated with significant toxicities. Evidence is sparse regarding the optimum LD regimen for TCR-T cell therapy in solid tumours.
METHODS
A systematic review was conducted of interventional, prospective clinical trials describing LD practices prior to TCR-T cell therapy in patients with advanced solid tumours. The objective was to define LD regimens administered prior to TCR-T cell therapy and their effects on specific safety and efficacy outcomes in this patient population.
RESULTS
Searches returned 484 studies, 19 (231 patients) met the eligibility criteria. Cyclophosphamide (cyclo) 60 mg/kg daily (2 days), plus fludarabine (fludara) 25 mg/m daily (5 days) was the most common LD regimen (38% of studies). Higher dose LD regimens were associated with increased pooled incidence rates of febrile neutropaenia compared to low dose (0.64, [95% Confidence interval (CI): 0.50-0.78], vs. 0.39 [95% CI: 0.25-0.53], respectively) but were not significantly associated with higher objective responses (odds ratio: 1.05, 95%CI: 0.60-1.82, p = 0.86). A major shortfall in safety data reporting was identified; determination of LD regimen effects on many safety outcomes was not possible.
CONCLUSION
Standard consensus guidelines for the design and reporting of adoptive cell therapy (ACT) studies would facilitate accurate risk-benefit analysis for optimising LD regimens in patients with advanced solid tumours.
Topics: Humans; Prospective Studies; Neoplasms; Cyclophosphamide; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 36315268
DOI: 10.1007/s00262-022-03287-1 -
Life (Basel, Switzerland) Oct 2022Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present... (Review)
Review
Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword "alpha-phellandrene" in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species and are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.
PubMed: 36295037
DOI: 10.3390/life12101602 -
International Journal of Environmental... Oct 2022Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of... (Review)
Review
Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of absorbed xenobiotics. Through a search of relevant databases, this systematic review gathers and critically discusses the published papers (excluding other types of publications) from 2001-2021 that have assessed urinary mutagenicity (Ames test with ) in an occupational exposure context. Due to the heterogeneity of the study methods, a meta-analysis could not be conducted. The characterized occupations were firefighters, traffic policemen, bus drivers, mail carriers, coke oven and charcoal workers, chemical laboratory staff, farmers, pharmacy workers, and professionals from several other industrial sectors. The genetically modified bacterial strains (histidine dependent) TA98, TA100, YG1041, YG1021, YG1024 and YG1042 have been used for the health risk assessment of individual (e.g., polycyclic aromatic hydrocarbons) and mixtures of compounds (e.g., diesel engine exhaust, fire smoke, industrial fumes/dyes) in different contexts. Although comparison of the data between studies is challenging, urinary mutagenicity can be very informative of possible associations between work-related exposure and the respective mutagenic potential. Careful interpretation of results and their direct use for occupational health risk assessment are crucial and yet complex; the use of several strains is highly recommended since individual and/or synergistic effects of complex exposure to xenobiotics can be overlooked. Future studies should improve the methods used to reach a standardized protocol for specific occupational environments to strengthen the applicability of the urinary mutagenicity assay and reduce inter- and intra-individual variability and exposure source confounders.
Topics: Humans; Mutagens; Mutagenicity Tests; Coke; Charcoal; Histidine; Vehicle Emissions; Polycyclic Aromatic Hydrocarbons; Smoke; Coloring Agents
PubMed: 36293654
DOI: 10.3390/ijerph192013074 -
Frontiers in Nutrition 2022Clinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat...
BACKGROUND
Clinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat are involved in the pathogenesis of human cancer. Here we conducted a systematic review and meta-analysis to examine whether meat mutagens [PhIP, MeIQx, DiMeIQx, total HCA, and B(a)P] present a risk factor for human cancer.
METHODS
We searched the following databases for relevant articles published from inception to 10 Oct 2021 with no language restrictions: Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Baidu Academic, Zhejiang Digital Library. Two independent researchers screened all titles and obtained eligible texts for further screening. Independent data extraction was conducted, and meta-analysis was carried out using random-effects models to calculate the risk ratio of the meat mutagens exposure.
RESULTS
A total of 1,786,410 participants and 70,653 cancer cases were identified. Among these, there were 12 different types of cancer at various sites, i.e., breast, bladder, colorectal, colon, rectum, prostate, lung, Non-Hodgkin lymphoma, kidney, gastric, esophagus, pancreatic, hepatocellular carcinoma. Cancer risk was significantly increased by intake of PhIP (OR = 1.13;95% CI 1.07-1.21; < 0.001), MeIQx (OR = 1.14; 95% CI: 1.07-1.21; < 0.001), DiMeIQx (OR = 1.07; 95% CI: 1.01-1.13; = 0.013), total HCA (OR = 1.20; 95% CI: 1.03-1.38; = 0.016), and cancer risk was not significantly increased by intake of B(a)P (OR = 1.04; 95% CI: 0.98-1.10; = 0.206).
CONCLUSION
Meat mutagens of PhIP, MeIQx, DiMeIQx, and total HCA have a positive association with the risk of cancer.
SYSTEMATIC REVIEW REGISTRATION
[www.crd.york.ac.uk/prospero], identifier [CRD42022148856].
PubMed: 36211500
DOI: 10.3389/fnut.2022.962688 -
Oxidative Medicine and Cellular... 2022Chagas disease is an anthropozoonosis caused by the protozoan and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American... (Review)
Review
Chagas disease is an anthropozoonosis caused by the protozoan and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American continent, including Bolivia, Argentina, and Paraguay. Unfortunately, there are no optimally effective treatments that can reduce the damage caused in the digestive form of the disease, such as the neuronal destruction of the myenteric plexus of both the esophagus and the colon. Therefore, the objective of this systematic review was to report the possible pharmacological neuroprotective agents that were tested in murine models of the digestive form of Chagas disease. Inclusion criteria are experimental studies that used different murine models for digestive forms of Chagas disease related to pharmacological interventions with neuroprotective potential, without year and language restriction. On the other hand, the exclusion criteria were studies that did not approach murine models with the digestive form of the disease or did not use neuroprotective treatments, among others. The search in the PubMed, Web of Science, Embase, and LILACS databases was performed on September 4, 2021. In addition, a manual search was performed using the references of the included articles. The risk of bias assessment of the studies was performed based on the SYRCLE tool guidelines, and the data from the selected articles are presented in this review as a narrative description and in tables. Eight articles were included, 4 of which addressed treatment with acetylsalicylic acid, 3 with cyclophosphamide, and 1 with Lycopodium clavatum 13c. In view of the results of the studies, most of them show neuroprotective activity of the treatments, with the potential to reduce the number of damaged neurons, as well as positive changes in the structure of these cells. However, more studies are needed to understand the mechanisms triggered by each drug, as well as their safety and immunogenicity. Systematic review registration is as follows: PROSPERO database (CRD42022289746).
Topics: Animals; Aspirin; Chagas Disease; Cyclophosphamide; Humans; Mice; Neuroprotective Agents; Trypanosoma cruzi
PubMed: 36199427
DOI: 10.1155/2022/9397290 -
Medicine Sep 2022Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and feasibility of R-CHOP and DA-EPOCH-R as the first-line therapy for patients with DEL is urgently needed.
METHODS
The clinical and treatment outcomes of 75 DEL patients were retrospectively analyzed. The role of DA-EPOCH-R was determined and compared to that of R-CHOP in DEL patients. PubMed, Embase, the Cochrane Central Library, and ClinicalTrials.gov were systematically searched up to November 1, 2021 and were evaluated by Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles comparing DA-EPOCH-R versus R-CHOP in patients with DEL were included.
RESULTS
Overall, 49 and 26 DEL patients received R-CHOP and DA-EPOCH-R, respectively. Although the difference in response for patients who received R-CHOP and DA-EPOCH-R was not significant (P = .347), DA-EPOCH-R may improve the prognosis compared to R-CHOP (P = .056 for progression-free survival [PFS], P = .009 for overall survival [OS]). A systematic review and meta-analysis including 412 DEL patients in six articles were conducted. The event rate for 3-year PFS was significantly lower in patients receiving DA-EPOCH-R treatment than in those undergoing R-CHOP treatment (OR = 0.63, 95% CI = 0.42-0.94, P = .02), whereas no statistically significant difference was found in the HRs for both PFS and OS or the event rate for 3-year OS.
CONCLUSION
The results of this study indicated that DA-EPOCH-R might improve the prognosis of DEL patients compared with R-CHOP.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prognosis; Retrospective Studies; Rituximab; Vincristine
PubMed: 36197215
DOI: 10.1097/MD.0000000000030620 -
Particle and Fibre Toxicology Sep 2022The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union... (Review)
Review
The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union (EU) funded projects have increased during the last decade. In parallel, large research efforts have contributed to both our understanding of key physico-chemical (PC) parameters regarding NM characterization as well as the limitations of toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all of these data are reliable or relevant from the regulatory perspective. The aim of this systematic review is to investigate the extent of studies on genotoxicity of NMs that can be considered reliable and relevant by current standards and bring focus to what is needed for a study to be useful from the regulatory point of view. Due to the vast number of studies available, we chose to limit our search to two large groups, which have raised substantial interest in recent years: nanofibers (including nanotubes) and metal-containing nanoparticles. Focusing on peer-reviewed publications, we evaluated the completeness of PC characterization of the tested NMs, documentation of the model system, study design, and results according to the quality assessment approach developed in the EU FP-7 GUIDEnano project. Further, building on recently published recommendations for best practices in nanogenotoxicology research, we created a set of criteria that address assay-specific reliability and relevance for risk assessment purposes. Articles were then reviewed, the qualifying publications discussed, and the most common shortcomings in NM genotoxicity studies highlighted. Moreover, several EU projects under the FP7 and H2020 framework set the aim to collectively feed the information they produced into the eNanoMapper database. As a result, and over the years, the eNanoMapper database has been extended with data of various quality depending on the existing knowledge at the time of entry. These activities are highly relevant since negative results are often not published. Here, we have reviewed the NanoInformaTIX instance under the eNanoMapper database, which hosts data from nine EU initiatives. We evaluated the data quality and the feasibility of use of the data from a regulatory perspective for each experimental entry.
Topics: DNA Damage; Databases, Factual; Metal Nanoparticles; Nanostructures; Reproducibility of Results
PubMed: 36104711
DOI: 10.1186/s12989-022-00499-2 -
Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081