Search Results (187)

Boron-containing compounds (BCCs) have emerged as potential drugs. Their drug-like effects are mainly explained by their mechanisms of action in enzymes. Nowadays, some experimental data support the effects of specific BCCs on GPCRs, provided there are crystal structures that show them bound to G protein-coupled receptors (GPCRs). Some BCCs are recognized as potential ligands of GPCRs—the drug targets of many diseases. Objective: The aim of this study was to collecte up-to-date data on the interactions of BCCs with GPCRs. Methods: Data were collected from the National Center of Biotechnology Information, PubMed, Global Health, Embase, the Web of Science, and Google Scholar databases and reviewed. Results: Some experimental reports support the interactions of BCCs with several GPCRs, acting as their labels, agonists, or antagonists. These interactions can be inferred based on in silico and in vitro results if there are no available crystal structures for validating them. Conclusions: The actions of BCCs on GPCRs are no longer hypothetical, as the existing evidence supports BCCs’ interactions with and actions on GPCRs. Full article

The distribution of Amaryllidaceae alkaloids, with a focus on their chemodiversity, has been reported previously, but not at a genera-wide diversity level. This review provides a comprehensive survey of the occurrence of Amaryllidaceae alkaloids across the genera of the Amaryllidaceae family. This survey is taxonomically guided by the National Center for Biotechnology Information (NCBI) Taxonomy Browser, with targeted keyword searches conducted in the Chemical Abstracts Service (CAS) SciFinder-n and PubMed. The family Amaryllidaceae comprises over 1214 species across three subfamilies: Agapanthoideae (1 genus, 5 species), Allioideae (3 genera plus 11 subgenera, 617 species), and Amaryllidoideae (58 genera plus 13 subgenera, 592 species). Amaryllidaceae alkaloids have been identified exclusively in 36 of the 58 genera and 6 of the 13 subgenera within the Amaryllidoideae subfamily. To date, more than 600 Amaryllidaceae alkaloids have been isolated, predominantly from this subfamily—hence the designation “Amaryllidaceae alkaloids”. These alkaloids display a wide spectrum of biological activities, including acetylcholinesterase inhibition, anti-inflammatory, antioxidant, antimicrobial, antidiabetic, and anticancer effects. A notable example is galanthamine (also known as galantamine), an FDA-approved drug marketed under the brand names Reminyl™ (Janssen Research Foundation, Beerse, Belgium, 2001) and Razadyne™ (Johnson & Johnson Pharmaceutical Research, New Brunswick, NJ, USA, 2004) for the treatment of mild to moderate Alzheimer’s disease, due to its potent acetylcholinesterase-inhibitory activity. Galanthamine has been isolated from species belonging to the genera Cyrtanthus, Galanthus, Leucojum, Lycoris, Narcissus, Ungernia, Chlidanthus, Crinum, Eucharis, Eustephia, Pancratium, and Phaedranassa. Lycorine is another widely distributed alkaloid found across multiple genera, and it has been extensively studied for its diverse bioactivities. Given the remarkable chemical diversity and bioactivity of Amaryllidaceae alkaloids, along with the many underexplored genera and species, further research into Amaryllidaceae species and their alkaloids is strongly warranted to support the discovery and development of novel therapeutic agents. Full article

Muscle is a crucial component of cattle, playing a vital role in determining the final quality of beef. This study aimed to identify candidate genes associated with muscle growth and lipid metabolism in beef and dairy cattle by utilizing the public database of the National Center for Biotechnology Information (NCBI) to download bovine muscle transcriptome data. Through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and SHapley Additive exPlanation (SHAP) explains machine learning models, we integrated and screened for relevant genes. The results showed a total of 2588 differentially expressed genes (DEGs), with 933 upregulated and 1655 downregulated in beef cattle compared to dairy cattle. In the WGCNA, the purple, black, green, red, brown, and blue modules were identified as significant modules. Based on the results of five different machine learning models, the Adaptive Boosting (AdaBoost) model demonstrated superior classification performance (accuracy = 0.84) compared to the other four models and was therefore selected as the optimal model. SHAP analysis was then employed to interpret the results, yielding the top 500 SHAP genes. In combination with DEGs and WGCNA, a total of 117 genes were identified. Subsequent functional enrichment analysis of these 117 genes revealed significant enrichment in pathways such as lipoprotein metabolic process, muscle contraction, and cytoskeleton in muscle cells, followed by interaction network analysis of genes and pathways. Ultimately, the APOA1, ACTB, S1PR1, PKLR, and SLC27A6 genes were identified as potential key regulators of lipid metabolism and muscle growth in beef and dairy cattle. In summary, this study provides a feasible method for handling large-scale transcriptome data and lays a foundation for future research on meat quality and improving the economic benefits of Holstein cattle. Full article

Since the first bacterial genomes were sequenced and annotated over 25 years ago, sequencing technologies have rapidly advanced in both speed and cost efficiency. To date, over two million annotated bacterial genomes have been deposited in the National Center for Biotechnology Information (NCBI) database. Yet, there are many genes with unknown functions and, furthermore, conflicting results have been published for many investigated genes. One example is the ratA (or pasT) gene from Escherichia coli (E. coli) K-12 strains. Initially identified as a ribosome-targeting toxin, later studies described RatA as the bacterial homolog of the mitochondrial Coq10 protein and, therefore, beneficial for E. coli cells during aerobic growth. This study shows that these conflicting results originated from a mis-annotation of the start codon in the genomic sequence. Overexpression of the ratA gene as currently annotated leads to the synthesis of two RatA protein variants, a toxic and a non-toxic one. This study further identifies the endogenous ratA promoter and shows that only the shorter, non-toxic variant of RatA is synthesized during different growth phases specifically under aerobic conditions. Our findings thereby not only solidify the role of RatA in E. coli, but also demonstrate the importance of first validating the basics of molecular biology when investigating a previously poorly described gene, even in times of advanced high-throughput techniques. Full article

Background: The NAC transcription factor family of genes is one of the largest families of transcription factors in plants, playing important functions in plant growth and development, response to adversity stress, disease resistance, and hormone signaling. In this study, we identified the number of members of the Panax notoginseng NAC (PnNAC) gene family and conducted a comprehensive analysis of their physicochemical characteristics, chromosomal location, evolutionary features, and expression patterns both in different parts of the plant at different growth stages and in response to infection by Alternaria panax. Methods: The NAC gene family in P. notoginseng was identified using Hidden Markov Model (HMMER) and National Center of Biotechnology Information Conserved Domain Database (NCBI CDD), and their physicochemical properties were analyzed with Perl scripts. Phylogenetic relationships were determined using Clustal Omega and FastTree, and gene structures were visualized with an R script. Promoter regions were analyzed with PlantCARE, motifs with MEME and ggmotif, and transcriptome data were processed using Hical Indexing for Spliced Alignment of Transcripts (HISAT2) and HTseq. Results: This study identified 98 PnNAC genes in P. notoginseng, analyzed their characteristics (protein lengths 104–882 aa, molecular weights 11.78–100.20 kDa, isoelectric points 4.12–9.75), location (unevenly distributed on 12 chromosomes, no tandem repeats), evolution, and expression patterns (distinct in different parts, growth stages, and after A. panax infection). Conclusions: PnNAC plays an important role in the growth and development of P. notoginseng and in its response to A. panax. PnNAC could be a candidate gene for further research on and functional analysis of P. notoginseng disease resistance. Full article

Background/Objectives: To systematically evaluate scientific evidence related to the influence of psychological stress on the response to periodontal treatment. Methods: PubMed/NCBI (National Center for Biotechnology Information, US National Library of Medicine), Web of Science (ClarivateTM), EBSCOHost, SCOPUS, and ProQuest databases were searched for published clinical studies in English up to May 2024. The quality of each study was assessed using the Ottawa–Newcastle scale. Results: Of 803 relevant articles identified, 8 were included in the qualitative synthesis qualitative synthesis. These studies involved 445 patients who completed the follow-up period, ranging from 6 weeks to 6 months. Stressed patients were more likely to experience higher levels of PPD and BOP compared to non-stressed patients. In total, 75% of the included studies showed a positive relationship between stress and response to NSPT, 12.5% observed a negative relationship, and the remaining 12.5% found some degree of relationship in the results of clinical periodontal parameters. The level of evidence is categorized according to the quality of the synthesis presented. Conclusions: There is a positive correlation between psychological stress and periodontal treatment response, indicating that stress may negatively influence the clinical outcomes of NSPT. Stress may reduce the inflammatory response, which is crucial for eliminating periodontal micropathogens after periodontal treatment. Full article

Background: The phylogenetic resolution within the Gloydius halys-intermedius Complex remains debatable due to the following reasons: loci selection in previous studies varied between authors; limited dataset (1−5 mitochondrial or nuclear gene fragments); lack of sampling density; and nodal supports at specific nodes remain weak, specifically within Gloydius cognatus, G. halys, and G. stejnegeri. Objectives: To revise the taxonomic and phylogenetic relationships within the G. halys-intermedius Complex, we reconstructed the molecular phylogeny and performed species delimitation based on the complete mitochondrial genomes. Methods: In this study, twelve nomenclatural groups of Gloydius species were involved in the computation of Bayesian phylogenomic inference, five of the twelve nomenclature groups were newly sequenced, while the rest were acquired from the National Center for Biotechnology Information (NCBI). The Bayesian phylogenomic inference was constructed based on 13 mitochondrial protein-coding genes. Species delimitation was performed by two distance-based methods (ABGD and ASAP) and two tree-based methods (GMYC and bPTP). Results: This research resolved the systematic relationship within the G. intermedius Complex with the support of mitogenome-based phylogenomics, while indicating cryptic diversity within the Gloydius halys-intermedius Complex: G. intermedius samples from South Korea show as paraphyletic to the cluster of the samples from northeastern China. Species delimitation results based on four models resemble each other, supporting Gloydius caucasicus, G. cognatus, G. halys, and G. stejnegeri, each representing full species. The species delimitation results of this research also resemble the nomenclatural species based on previous morphometrical results. This research indicates that species delimitation efforts based on the phylogenomic approach would likely resolve complex evolutionary relationships. Full article

Resveratrol, a plant-derived polyphenol, exhibits significant antidepressant effects and notably enhances neuroplasticity in neurological diseases. However, whether the antidepressant function of resveratrol is related to neuroplasticity remains uncertain, and the underlying mechanisms is poorly understood. This study aims to investigate the role and mechanism of resveratrol in neuroplasticity in depression. Here, we adopted the chronic unpredictable mild stress (CUMS) model and resveratrol intervention by oral gavage. Thereafter, behavioral tests confirmed resveratrol’s antidepressant effect, and Nissl staining, Golgi staining, and Western blotting (WB) were employed to assess the neuronal plasticity. Moreover, proteomic analysis and WB were used to screen and identify the key proteins. To investigate the downstream target of ELAV-like RNA-binding protein 4 (ELAVL4) (one of candidate genes), the RNA Interactome Database and the National Center for Biotechnology Information databases were utilized to predict the targets of ELAVL4. Finally, Quantitative PCR, WB, and Immunofluorescence were used to verify the prediction. Our results indicate that resveratrol alleviates CUMS-induced depressive-like behaviors accompanied by the restoration of impaired hippocampal neuroplasticity. Then, proteomic analysis shows that 351 differentially expressed proteins (DEPs) decrease after CUMS, while 24 DEPs increase remarkably with the resveratrol treatment. Among which, ELAVL4 is downregulated by CUMS, simultaneously increasing after resveratrol intervention, which acts as a protective protein in this process. Finally, brain-derived neurotrophic factor (Bdnf) mRNA is predicted to be the potential target of ELAVL4 and validated by molecular technologies. In conclusion, our findings demonstrate that resveratrol’s antidepressant efficacy is closely associated with ELAVL4, an RNA-binding protein, a mediated neuroplasticity pathway, potentially intersecting with the Bdnf mRNA. Overall, this research sheds light on the role of the ELAVL4-Bdnf mRNA pathway through neuroplasticity in resveratrol’s antidepressant action, which provides an mRNA regulation perspective for the development of novel antidepressants and understanding depression pathology. Full article

Background: Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have the potential for self-renewal and a strong proliferative capacity, and sustain tumorigenesis capabilities. This ability of CSCs to escape immune responses makes the CSCs a primary source of functionally altered, immune-resistant, chemoresistant, aggressive tumor cells. These characteristics determine the potential advantage of targeting CSCs for the treatment of solid tumors. Method: First, we downloaded different gene expression datasets of CSCs from the NCBI-GEO (National Center for Biotechnology Information–Gene Expression Omnibus) database and identified common genes by using a suitable Venn tool. Subsequently, we explored the prognostic significance of the particular genes in particular cancers and analyzed the expression of these genes at the protein level in human solid tumors by using KM plotter (Kaplan-Meier plotter) and an HPA (The Human Protein Atlas) database, respectively. Finally, using a comparative toxicogenomic database, we selected several important drugs or chemicals. Result: From this study, we identified APOC1 as a common upregulated gene in breast cancer and SLC44A5 and CAV2 as common up- and downregulated genes in lung cancer. In ovarian cancer, PRRG4 is a commonly upregulated gene, and ADCY7, AKAP12, TPM2, and FLNC are commonly downregulated genes. These genes also show prognostic significance in respective cancers. Several drugs that are capable of targeting the expression or signaling network of designated genes of CSC were also identified, which may contribute in CSC-targeted cancer therapy. Conclusion: Our study suggests a need for more in-depth experimental investigations to determine the actual functional activity and the mechanism of action of these CSC-associated genes. Full article

Well-annotated gene and genomic sequences serve as a foundation for making inferences in molecular biology and evolution and can directly impact public health. The first SARS-CoV-2 genome was submitted to the GenBank database hosted by the U.S. National Center for Biotechnology Information and used to develop the two successful vaccines. Conserved protein domains are often chosen as targets for developing antiviral medicines or vaccines. Mutation and substitution patterns provide crucial information not only on functional motifs and genome/protein interactions but also for characterizing phylogenetic relationships among viral strains. These patterns, together with the collection time of viral samples, serve as the basis for addressing the question of when and where the host-switching event occurred. Unfortunately, viral genomic sequences submitted to GenBank undergo little quality control, and critical information in the annotation is frequently changed without being recorded. Researchers often have no choice but to hold blind faith in the authenticity of the sequences. There have been reports of incorrect genome annotation but no report that casts doubt on the genomic sequences themselves because it seems theoretically impossible to identify genomic sequences that may not be authentic. This paper takes an innovative approach to show that some SARS-CoV-2 genomes submitted to GenBank cannot possibly be authentic. Specifically, some SARS-CoV-2 genomic sequences deposited in GenBank with collection times in 2023 and 2024, isolated from saliva, nasopharyngeal, sewage, and stool, are identical to the reference genome of SARS-CoV-2 (NC_045512). The probability of such occurrence is effectively 0. I also compile SARS-CoV-2 genomes with changed sample collection times. One may be led astray in bioinformatic analysis without being aware of errors in sequences and sequence annotation. Full article

Background: Diarrhea frequently occurs after vascular organ transplantation, including kidney transplants. This may result from non-infectious factors, adverse effects of immunosuppressive medications, or infections caused by various pathogens, including viruses, bacteria, fungi, or parasites, for example, intestinal protozoan parasites such as Cryptosporidium spp., which are particularly dangerous for immunocompromised patients. Methods: This review is based on scientific articles sourced from validated databases such as PubMed, the National Center for Biotechnology Information (NCBI), ScienceDirect, and Google Scholar. The primary search was conducted on 12–13 July 2024, using the keywords ‘Cryptosporidium’ AND ‘cryptosporidiosis’ AND ‘kidney’ AND ‘transplant’ AND ‘adult’. Inclusion criteria encompassed human studies, case reports, peer-reviewed journal publications, review articles, and research articles in English. Exclusion criteria included studies not in English, gray literature (e.g., conference proceedings and abstracts), and data related to pediatric patients (under 18 years old) and HIV patients. Results: This systematic review and meta-analysis have highlighted an often-overlooked connection between Cryptosporidium spp. infections in adult kidney transplant recipients (KTR). Furthermore, it includes an analysis of the clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in these patients, based on available case reports. Our study demonstrates that adult kidney transplant patients are at a significantly higher risk of acquiring Cryptosporidium spp. compared to healthy participants. Conclusions: Cryptosporidium spp. infections can be asymptomatic, making it essential to screen both symptomatic and asymptomatic kidney transplant recipients. The clinical presentation of cryptosporidiosis typically involves digestive symptoms and can be complicated by biliary tract involvement. In KTR patients presenting with diarrhea, it is crucial to not only test for Cryptosporidium spp. but also to rule out bacterial and viral etiologies, including infections such as C. difficile, C. colitis, Clostridium spp., and rotavirus. The diagnosis of Cryptosporidium spp. infections primarily relies on microscopic methods, which are known for their low sensitivity. Therefore, diagnostic approaches should include both direct methods and, where possible, molecular techniques. Based on the analyzed cases, the most effective treatment results were achieved with reduction in immunosuppression if possible (strong, very low) and nitazoxanide at a dose of 500 mg twice daily for 14 days. Considering the public health implications of our findings, the current epidemiological data underscore the need for further research to develop effective prevention and intervention strategies against cryptosporidiosis. Preventive measures, regular screening programs, and the treatment of Cryptosporidium spp. infections should be integrated into the clinical care of transplant patients. It is also important that patients are informed about environmental risk factors. Full article

Introduction: Secondary complex microsurgical reconstructions after amputation and severe trauma injuries are often necessary to optimize functional outcomes. Methods and Patients: We reviewed eight patients who underwent extensive reconstruction after severe trauma. The details of secondary procedures are further described in the article. A literature search was performed using the National Center for Biotechnology Information (NCBI) database for studies evaluating secondary procedures after complex reconstructions. Discussion: To date, the order and the need for performing secondary procedures have yet to be fully defined. The tissues encountered include skin, soft tissue, bone, nerve, joint, and tendon. Conclusions: We described the use of a decision-theoretic approach to the secondary reconstruction. Treatment of a complex trauma should be measured by functional outcome. Full article

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p > 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; p = 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL; p = 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics. Full article

The short and long statistical correlations are essential in the genomic sequence. Such correlations are long-range for introns, whereas, for exons, these are short. In this study, we employed superstatistics to investigate correlations and fluctuations in the distribution of nucleotide sequence lengths of the Cucurbitaceae family. We established a time series for exon sizes to probe these correlations and fluctuations. We used data from the National Center for Biotechnology Information (NCBI) gene database to extract the temporal evolution of exon sizes, measured in terms of the number of base pairs (bp). To assess the model’s viability, we utilized a timescale extraction method to determine the statistical properties of our time series, including the local distribution and fluctuations, which provide the exon size distributions based on the q-Gamma and inverse q-Gamma distributions. From the Bayesian statistics standpoint, both distributions are excellent for capturing the correlations and fluctuations from the data. Full article

The United States of America (US) has the highest annual number of human babesiosis cases caused by Babesia microti (Bm). Babesia, like malaria-causing Plasmodium, are protozoan parasites that live within red blood cells (RBCs). Both infectious diseases can be associated with hemolysis and organ damage, which can be fatal. Since babesiosis was made a nationally notifiable condition by the Centers for Disease Control and Prevention (CDC) in January 2011, human cases have increased, and drug-resistant strains have been identified. Both the Bm ligand(s) and RBC receptor(s) needed for invasion are unknown, partly because of the difficulty of developing a continuous in vitro culture system. Invasion pathways are relevant for therapies (e.g., RBC exchange) and vaccines. We hypothesize that there is at least one RBC surface antigen that is essential for Bm invasion and that all Bm hosts express this. Because most RBC surface antigens that impact Plasmodium invasion are in human blood group (hBG) systems, which are generated by 51 genes, they were the focus of this study. More than 600 animals with at least one hBG system gene ortholog were identified using the National Center for Biotechnology Information (NCBI) command-line tools. Google Scholar searches were performed to determine which of these animals are susceptible to Bm infection. The literature review revealed 28 Bm non-human hosts (NHH). For 5/51 (9.8%) hBG system genes (e.g., RhD), no NHH had orthologs. This means that RhD is unlikely to be an essential receptor for invasion. For 24/51 (47.1%) hBG system genes, NHH had 4–27 orthologs. For the ABO gene, 15/28 NHH had an ortholog, meaning that this gene is also unlikely to generate an RBC antigen, which is essential for Bm invasion. Our prior research showed that persons with blood type A, B, AB, O, RhD+, and RhD- can all be infected with Bm, supporting our current study’s predictions. For 22/51 (43.1%) hBG system genes, orthologs were found in all 28 NHH. Nineteen (37.3%) of these genes encode RBC surface proteins, meaning they are good candidates for generating a receptor needed for Bm invasion. In vitro cultures of Bm, experimental Bm infection of transgenic mice (e.g., a CD44 KO strain), and analyses of Bm patients can reveal further clues as to which RBC antigens may be essential for invasion. Full article