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European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Cancers Sep 2022Deregulation of conventional protein kinases is associated with the growth and development of cancer cells. Alpha-kinase 1 (ALPK1) belongs to a newly discovered family... (Review)
Review
BACKGROUND
Deregulation of conventional protein kinases is associated with the growth and development of cancer cells. Alpha-kinase 1 (ALPK1) belongs to a newly discovered family of serine/threonine protein kinases with no sequence homology to conventional protein kinases, and its function in cancer is poorly understood.
METHODS
In this systematic review, we searched for and analyzed studies linking ALPK1 to cancer development and progression.
RESULTS
Based on the current evidence obtained using human, animal, cellular, and tissue models, ALPK1 is located upstream and triggers cancer cell development and metastasis by regulating the inflammatory response through phosphorylation. Its mRNA and protein levels were found to correlate with advanced tumor size and lymph node metastasis, which occur from the cellular cytoplasm into the nucleus. ALPK1 is also strongly associated with gout, chronic kidney disease, and diabetes, which are considered as inflammatory diseases and associated with cancer.
CONCLUSION
ALPK1 is an oncogene involved in carcinogenesis. Chronic inflammation is the common regulatory mechanism between cancer and these diseases. Future research should focus on identifying inhibitors of serine/threonine and ALPK1 at their phosphorylation sites, which would block various signal transductions and potentially offer kinase-targeted therapeutic agents for patients with cancer and inflammatory diseases.
PubMed: 36139553
DOI: 10.3390/cancers14184390 -
Frontiers in Genetics 2022Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes...
Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes improve the cropping environment by replenishing the soil nitrogen content. Chickpeas are the second most significant staple legume food crop worldwide behind dry bean which contains 17%-24% protein, 41%-51% carbohydrate, and other important essential minerals, vitamins, dietary fiber, folate, β-carotene, anti-oxidants, micronutrients (phosphorus, calcium, magnesium, iron, and zinc) as well as linoleic and oleic unsaturated fatty acids. Despite these advantages, legumes are far behind cereals in terms of genetic improvement mainly due to far less effort, the bottlenecks of the narrow genetic base, and several biotic and abiotic factors in the scenario of changing climatic conditions. Measures are now called for beyond conventional breeding practices to strategically broadening of narrow genetic base utilizing chickpea wild relatives and improvement of cultivars through advanced breeding approaches with a focus on high yield productivity, biotic and abiotic stresses including climate resilience, and enhanced nutritional values. Desirable donors having such multiple traits have been identified using core and mini core collections from the cultivated gene pool and wild relatives of Chickpea. Several methods have been developed to address cross-species fertilization obstacles and to aid in inter-specific hybridization and introgression of the target gene sequences from wild species. Additionally, recent advances in "Omics" sciences along with high-throughput and precise phenotyping tools have made it easier to identify genes that regulate traits of interest. Next-generation sequencing technologies, whole-genome sequencing, transcriptomics, and differential genes expression profiling along with a plethora of novel techniques like single nucleotide polymorphism exploiting high-density genotyping by sequencing assays, simple sequence repeat markers, diversity array technology platform, and whole-genome re-sequencing technique led to the identification and development of QTLs and high-density trait mapping of the global chickpea germplasm. These altogether have helped in broadening the narrow genetic base of chickpeas.
PubMed: 36035111
DOI: 10.3389/fgene.2022.905771 -
Frontiers in Medicine 2022Baduanjin (BDJ) exercise is a traditional exercise that combines breathing, body movement, meditation and awareness to help delay the onset and progression of senile...
PURPOSE
Baduanjin (BDJ) exercise is a traditional exercise that combines breathing, body movement, meditation and awareness to help delay the onset and progression of senile degenerative musculoskeletal diseases, such as osteoporosis (OP). The aim of this meta-analysis is to evaluate the efficacy of BDJ exercise, and preliminarily infer its effective mechanism in the treatment of OP.
METHODS
We identified relevant randomized controlled trials (RCTs) through eight databases, and compared BDJ exercise with the control groups (including blank control and conventional treatment intervention). The main outcome measure was bone mineral density (BMD), the additional outcome measures were visual analogue scale (VAS), Berg balance scale (BBS), serum Calcium (Ca), serum Phosphorus (P), serum Alkaline phosphatase (ALP), and serum bone gla protein (BGP). Meta-analysis and trial sequence analysis (TSA) were performed using RevMan 5.4, Stata 16.0, and TSA 0.9.
RESULTS
In total, 13 RCTs involving 919 patients were included in the analysis. For postmenopausal osteoporosis, BDJ exercise alone and BDJ exercise combined with conventional treatment can improve the BMD of lumbar spine. BDJ exercise alone can influence serum Ca and ALP. BDJ exercise combined with conventional treatment can improve balance (BBS) and influence serum BGP. For senile osteoporosis, BDJ exercise alone and BDJ exercise combined with conventional treatment can improve balance (BBS). BDJ exercise combined with conventional treatment can improve the BMD of hip and pain relieve (VAS). For primary osteoporosis, BDJ exercise combined with conventional treatment can improve the BMD of lumbar spine and femoral neck.
CONCLUSION
Baduanjin exercise may be beneficial to improve BMD, relieve pain, improve balance ability, influence serum BGP and serum ALP in patients with OP, but differences occur due to various types of OP. Due to the low quality of research on the efficacy and mechanism of BDJ exercise in the treatment of OP, high-quality evidence-based research is still needed to provide reliable supporting evidence.
SYSTEMATIC REVIEW REGISTRATION
[http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022329022].
PubMed: 35991646
DOI: 10.3389/fmed.2022.935961 -
Biomarkers : Biochemical Indicators of... Dec 2022In patients with metastatic triple-negative breast cancer (TNBC), programmed death-ligand 1 (PD-L1) expression has been demonstrated to predict response to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In patients with metastatic triple-negative breast cancer (TNBC), programmed death-ligand 1 (PD-L1) expression has been demonstrated to predict response to immunotherapy. It is unclear whether PD-L1 expression measured with currently available validated assays can predict chemotherapy response in patients with non-metastatic TNBC.
METHODS
We conducted a systematic review and meta-analysis of clinical studies to assess the PD-L1 expression as a predictor of response to chemotherapy in non-metastatic TNBC using validated assays. The primary endpoint was pathological complete response (pCR) rate to neoadjuvant chemotherapy. Secondary endpoints included the prevalence of PD-L1 expression in non-metastatic TNBC and its impact on disease-free survival (DFS) and overall survival (OS). Moreover, RNA sequence data from the TCGA breast cancer cohort was used to define the relationship between expression and response to chemotherapy and prognosis.
RESULTS
Nineteen studies were eligible for the meta-analysis with a total of 2403 patients with non-metastatic TNBC disease. The PD-L1-positive cohort had a significantly higher likelihood of achieving pCR with neoadjuvant chemotherapy (pooled odds ratio = 1.95; 95% CI = 1.39-2.73, < 0.0001). In studies which reported long-term outcomes, PD-L1 positivity was associated with significantly better DFS and OS compared to PD-L1 negative patients (pooled hazard ratio = 0.51; 95% CI = 0.35-0.74, < 0.0001 and 0.51; 95% CI = 0.27-0.94, = 0.031, respectively). Transcriptomic data suggested that PD-L1 expression is a surrogate marker for the upregulation of key immune-related genes that mediate response to chemotherapy in TNBC.
CONCLUSION
This analysis clearly shows that patients with PD-L1 positive TNBC respond better to neoadjuvant chemotherapy and are associated with better survival outcomes compared to patients with PD-L1 negative tumours. The newly distinct quadruple negative breast cancer (QNBC) subtype should be defined as the BC subtype with the poorest outcome in the non-metastatic setting, highlighting the need for more aggressive therapy approaches.
Topics: Humans; B7-H1 Antigen; Triple Negative Breast Neoplasms; Neoadjuvant Therapy; Prognosis
PubMed: 35980714
DOI: 10.1080/1354750X.2022.2112614 -
Current Issues in Molecular Biology Dec 2021according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and... (Review)
Review
according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and deaths. From a preventive and therapeutic point of view, there are two concerns that affect institutions and healthcare professionals: global immunization (which is still far from being achieved) and the availability of drugs capable of preventing its consequences in the infected patient. In this sense, the role that melatonin can play is has been assessed in the recent literature. : the serious health, social and economic consequences of COVID-19 have forced an urgent search for preventive methods, such as vaccines, among others, and therapeutic methods that could be alternatives to the drugs currently used. In this sense, it must be accepted that one of the most recommended has been the administration of melatonin. The present study proposes to carry out a systematic review of its possible role in the treatment and/or prevention of COVID-19. : a systematic review of the literature related to the prevention of COVID-19 through the administration of melatonin was carried out, following the sequence proposed by the Prisma Declaration regarding the identification and selection of documents, using the specialized health databases Trip Medical Database, Cochrane Library, PubMed, Medline Plus, BVS, Cuiden and generic databases such as Dialnet, Web of Science and Google Scholar for their retrieval. Appropriate inclusion and exclusion criteria are described for the articles assessed. The main limitation of the study has been the scarcity of works and the lack of defining a specific protocol in terms of dosage and administration schedule. : once the selection process was completed, and after an in-depth critical analysis, 197 papers were selected, and 40 of them were finally used. The most relevant results were: (1) melatonin prevents SARS-CoV-2 infection, (2) although much remains to be clarified, at high doses, it seems to have a coadjuvant therapeutic effect in the treatment of SARS-CoV-2 infection and (3) melatonin is effective against SARS-CoV-2 infection. : until group immunization is achieved in the population, it seems clear that we must continue to treat patients with SARS-CoV-2 infection, and, in the absence of a specific and effective antiviral therapy, it is advisable to continue researching and providing drugs that demonstrate validity based on the scientific evidence. In this regard, we believe that the available studies recommend the administration of melatonin for its anti-inflammatory, antioxidant, immunomodulatory, sleep-inducing, CD147, Mpro, p65 and MMP9 protein suppressing, nephrotoxicity-reducing and highly effective and safe effects. : (1) melatonin has anti-inflammatory, antioxidant, immunomodulatory, and Mpro and MMP9 protein-inhibitory activity. (2) It has been shown to have a wide margin of safety. (3) The contributions reviewed make it an effective therapeutic alternative in the treatment of SARS-CoV-2 infection. (4) Further clinical trials are recommended to clearly define the administration protocol.
PubMed: 35723382
DOI: 10.3390/cimb44010003 -
Viruses May 2022Live-attenuated SARS-CoV-2 vaccines received relatively little attention during the COVID-19 pandemic. Despite this, several methods of obtaining attenuated...
Live-attenuated SARS-CoV-2 vaccines received relatively little attention during the COVID-19 pandemic. Despite this, several methods of obtaining attenuated coronaviruses are known. In this systematic review, the strategies of coronavirus attenuation, which may potentially be applied to SARS-CoV-2, were identified. PubMed, Scopus, Web of Science and Embase databases were searched to identify relevant articles describing attenuating mutations tested in vivo. In case of coronaviruses other than SARS-CoV-2, sequence alignment was used to exclude attenuating mutations that cannot be applied to SARS-CoV-2. Potential immunogenicity, safety and efficacy of the attenuated SARS-CoV-2 vaccine were discussed based on animal studies data. A total of 27 attenuation strategies, used to create 101 different coronaviruses, have been described in 56 eligible articles. The disruption of the furin cleavage site in the SARS-CoV-2 spike protein was identified as the most promising strategy. The replacement of core sequences of transcriptional regulatory signals, which prevents recombination with wild-type viruses, also appears particularly advantageous. Other important attenuating mutations encompassed mostly the prevention of evasion of innate immunity. Sufficiently attenuated coronaviruses typically caused no meaningful disease in susceptible animals and protected them from challenges with virulent virus. This indicates that attenuated COVID-19 vaccines may be considered as a potential strategy to fight the threat posed by SARS-CoV-2.
Topics: Animals; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccine Development; Vaccines, Attenuated
PubMed: 35632736
DOI: 10.3390/v14050991 -
Frontiers in Microbiology 2022Methicillin-resistant (MRSA) is a leading cause of hospital-associated (HA) and community-associated (CA) infections globally. The multi-drug resistant nature of this... (Review)
Review
BACKGROUND
Methicillin-resistant (MRSA) is a leading cause of hospital-associated (HA) and community-associated (CA) infections globally. The multi-drug resistant nature of this pathogen and its capacity to cause outbreaks in hospital and community settings highlight the need for effective interventions, including its surveillance for prevention and control. This study provides an update on the clonal distribution of MRSA in Africa.
METHODS
A systematic review was conducted by screening for eligible English, French, and Arabic articles from November 2014 to December 2020, using six electronic databases (PubMed, EBSCOhost, Web of Science, Scopus, African Journals Online, and Google Scholar). Data were retrieved and analyzed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (registered at PROSPERO: CRD42021277238). Genotyping data was based primarily on multilocus sequence types (STs) and Staphylococcal Cassette Chromosome (SCC) types. We utilized the Phyloviz algorithm in the cluster analysis and categorization of the MRSA STs into various clonal complexes (CCs).
RESULTS
We identified 65 studies and 26 publications from 16 of 54 (30%) African countries that provided sufficient genotyping data. MRSA with diverse staphylococcal protein A () and SCC types in CC5 and CC8 were reported across the continent. The ST5-IV [2B] and ST8-IV [2B] were dominant clones in Angola and the Democratic Republic of Congo (DRC), respectively. Also, ST88-IV [2B] was widely distributed across the continent, particularly in three Portuguese-speaking countries (Angola, Cape Verde, and São Tomé and Príncipe). The ST80-IV [2B] was described in Algeria and Egypt, while the HA-ST239/ST241-III [3A] was only identified in Egypt, Ghana, Kenya, and South Africa. ST152-MRSA was documented in the DRC, Kenya, Nigeria, and South Africa. Panton-Valentine leukocidin (PVL)-positive MRSA was observed in several CCs across the continent. The median prevalence of PVL-positive MRSA was 33% (ranged from 0 to 77%; = 15).
CONCLUSION
We observed an increase in the distribution of ST1, ST22, and ST152, but a decline of ST239/241 in Africa. Data on MRSA clones in Africa is still limited. There is a need to strengthen genomic surveillance capacity based on a "One-Health" strategy to prevent and control MRSA in Africa.
PubMed: 35591993
DOI: 10.3389/fmicb.2022.860436 -
Annals of Palliative Medicine Mar 2022At present, corneal transplantation has become the main surgical method for infectious keratitis. However, the rejection of corneal graft after operation leads to graft... (Meta-Analysis)
Meta-Analysis
BACKGROUND
At present, corneal transplantation has become the main surgical method for infectious keratitis. However, the rejection of corneal graft after operation leads to graft opacity, which is an important reason for the failure of transplantation. There is no unified conclusion whether the rejection can be reduced by matching human leucocyte antigen (HLA) before operation. The purpose of this meta-analysis is to explore the correlation between HLA locus matching and corneal transplantation rejection, so as to provide evidence-based medical evidence for clinical corneal transplantation in the treatment of infectious keratitis.
METHODS
Search English databases, such as PubMed, Medline, Embase and Evidence-based Medicine Library by computer; Chinese databases, such as China Biomedical Literature Database, China Knowledge Network (CNKI) database, Wanfang database, Weipu database, and Google Academic database. According to Cochrane Handbook 5.0 risk assessment table, two researchers made random sequence random allocation method, blind method, allocation scheme hiding, integrity of data results and quality score of research results. The bias risk evaluation of Rev Man 5.3 software was used to evaluate the risk bias of the references.
RESULTS
A total of 5 literatures were included, and 725 eyes underwent penetrating keratoplasty, all of which were randomized controlled trials (RCTs). The quality of the included articles was medium to high quality. A meta-analysis of four HLA-A matching articles showed odds ratio (OR) =0.28, 95% confidential interval (CI): (0.15, 0.51), significance test Z=4.08, P<0.0001, and the difference was statistically significant. Meta-analysis was performed on four HLA-B matching articles and showed OR =0.50, 95% CI: (0.27, 0.89), significance test Z=2.33, P=0.02, and the difference was statistically significant. Meta-analysis of four HLA-DR matching articles showed OR =0.69, 95% CI: (0.41, 1.17), significance test Z=1.39, P=0.17, and the difference was not statistically significant.
DISCUSSION
In patients with infectious keratitis undergoing corneal transplantation, preoperative matching of HLA-A, HLA-B, and HLA-DR sites played an important role in corneal transplantation. Preoperative HLA matching is of clinical significance.
Topics: Amino Acids; Corneal Transplantation; Graft Survival; HLA-DR Antigens; Histocompatibility Testing; Humans
PubMed: 35365041
DOI: 10.21037/apm-22-268 -
Anais Da Academia Brasileira de Ciencias 2022Hypertension is a factor that contributes to the risk of chronic diseases. The inhibition of angiotensin-I converting enzyme (ACE) is a useful therapeutic approach to...
Hypertension is a factor that contributes to the risk of chronic diseases. The inhibition of angiotensin-I converting enzyme (ACE) is a useful therapeutic approach to the hypertension treatment. The algae have been an alternative for the production of ACE inhibitory (ACEi) peptides from enzymatic hydrolysis due to their protein-rich biomass. The aim of this study was to systematically review the literature regarding the production, composition and activity of ACEi peptides derived from algae proteins. Systematic database searches identified 648 related articles. Among these, only 14 were selected according to the eligibility criteria to this review. Macroalgae are more studied than microalgae as sources of ACEi peptides. Furthermore, hydrolysates by thermolysin or bromelain exhibited the highest ACEi activity compared to other enzymes. The main features of the peptides with high ACE inhibition are low molecular weight, short amino acids sequence and non-competitive inhibition pattern. In vivo studies using hydrolysates and peptides derived from algae proteins showed antihypertensive activity in spontaneously hypertensive rats (SHR). Thus, it is suggested that ACEi peptides derived from algae can be considered as potential antihypertensive.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Antihypertensive Agents; Hypertension; Peptides; Rats
PubMed: 35319622
DOI: 10.1590/0001-3765202220201636