Biallelic loss-of-function variations in BTD cause profound biotinidase deficiency in an Indian patient.

BACKGROUND: Biotinidase deficiency (BD) is a rare, autosomal recessive metabolic disorder characterized by neurocutaneous symptoms. This study investigates a case of profound BD in an Indian infant and the underlying genetic basis. METHODS: A 10-month-old male presenting with seizures, hypotonia, ataxia, visual impairments, and developmental delay underwent biochemical and genetic analysis. Biotinidase activity was measured using an ELISA kit. Sanger sequencing of the biotinidase (BTD) gene was performed to identify genetic variations. In silico analysis was employed to assess the potential impact of the identified variants. RESULTS: The infant biotinidase activity was undetectable and its suggest profound biotinidase deficiency. Novel biallelic loss-of-function variations (c.903G > A and c.946 C > T) in the BTD gene were identified, leading to premature stop codons and truncated, non-functional protein fragments. CONCLUSION: This case expands our knowledge of BD genetic diversity and underscores the critical role of early diagnosis and newborn screening programs in managing this treatable condition.

The novel m6A writer methyltransferase 5 is a promising prognostic biomarker and associated with immune cell infiltration in oral squamous cell carcinoma.

BACKGROUND: Emerging research has identified the N6-methyladenosine (m6A) modification and its regulatory enzymes, including methyltransferase 5 (METTL5), as critical players in cancer biology. However, the role of METTL5 in oral squamous cell carcinoma (OSCC) remains poorly understood. MATERIALS AND METHODS: We conducted a comprehensive study to investigate the expression and implications of METTL5 in OSCC. We recruited 76 OSCC patients to analyze METTL5 mRNA and protein expression using RT-qPCR and western blot. Additionally, we analyzed METTL5 expression and its correlation with clinical features, patient prognosis, immune cell infiltration, and biological pathways using the TCGA-HNSCC dataset, which primarily consists of OSCC samples. RESULTS: Our findings revealed significant overexpression of METTL5 in OSCC tissues compared to normal tissues. The high expression of METTL5 is associated with advanced cancer stages, higher tumor grades, nodal metastasis, and poorer patient outcomes, indicating its involvement in cancer progression. In silico functional analysis revealed that METTL5 plays a role in multiple biological pathways, highlighting its importance in cancer biology. Moreover, METTL5 has complex relationships with immune regulatory genes, suggesting its potential role in shaping the tumor immune microenvironment. CONCLUSION: METTL5 is a promising candidate for the prognosis and therapeutic intervention of OSCC. Its overexpression in cancer tissues, association with clinical features, and intricate links to immune regulatory networks underscore its significance in this malignancy. This study contributes to a deeper understanding of the complex factors influencing OSCC, and provides a foundation for future research and potential clinical applications.

N6-methyladenosine-mediated overexpression of TREM-1 is associated with periodontal disease.

Periodontitis, a prevalent inflammatory disease, involves the destruction of tooth-supporting tissues. N6-methyladenosine (m6A) is a type of post-transcriptional modification that significantly influences gene and protein expression. It is involved in the regulation of various diseases, including those with an inflammatory component. This study investigates the potential role of m6A-mediated TREM-1 expression in the development of periodontitis. Clinical features and TREM-1 expression were assessed in periodontitis patients and healthy controls. LPS-stimulated human gingival fibroblasts (HGFs) were used to investigate m6A levels, m6A regulator METTL3, TREM-1, and inflammatory gene expression. In silico functional analysis explored TREM-1 interactions and functionalities. Periodontitis patients showed significantly elevated TREM-1 expression at both mRNA and protein levels. Predicted m6A motifs were present within the TREM-1 transcript. LPS stimulation of HGFs increased m6A content, METTL3, and TREM-1 expression, suggesting a potential link between m6A modification and TREM-1 regulation. Bioinformatic analysis revealed TREM-1 interaction with genes associated with periodontitis and its association with inflammatory pathways. This study suggests a potential role for METTL3-mediated m6A modification in regulating TREM-1 expression in periodontitis. Further investigation is needed to solidify this link and translate findings into clinical applications for improved periodontal health.

Aberrated PSMA1 expression associated with clinicopathological features and prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a globally prevalent cancer with significant mortality rates. OSCC a predominant subtype of head and neck squamous cell carcinoma (HNSCC), poses a substantial health burden. Despite advancements in diagnosis and therapy, OSCC prognosis remains poor. The 26S proteasome, a cellular protein degradation complex, is associated with cancer, including PSMA1, a proteasomal subunit, which is upregulated in various cancers. We analyzed PSMA1 expression using TCGA data, validated it in OSCC samples using real-time PCR, and explored its role through various databases. Tumor and adjacent normal tissues from OSCC patients were examined, and PSMA1 expression was analyzed. Survival analysis assessed the impact of PSMA1 on patient outcomes, while immune infiltration was examined using the TIMER database. GeneMANIA, STRING, and Metascape were utilized for gene interaction and pathway analysis. PSMA1 was significantly upregulated in OSCC and HNSCC. Its overexpression correlated with advanced clinicopathological features and poorer prognosis in HNSCC patients. PSMA1 expression is also related to immune cell infiltration. Gene interaction analysis revealed PSMA1 involvement in proteolysis regulation, suggesting its potential as a therapeutic target. PSMA1 upregulation in HNSCC association with adverse clinicopathological features and prognosis underscores its potential significance. Further research is warranted to elucidate its molecular mechanisms and therapeutic potential in OSCC management.

Increased SEC14L2 expression is associated with clinicopathological features and worse prognosis in oral squamous cell carcinoma.

Abnormal expression of SEC14L2 has been implicated in many human cancers. However, the role of SEC14L2 in oral squamous cell carcinoma (OSCC) remains unclear. Therefore, this study aimed to evaluate the expression and prognostic roles of SEC14L2 in OSCC. OSCC tumors and adjacent non-tumors were collected from OSCC patients and used for SEC14L2 mRNA expression by quantitative reverse transcription PCR (RT-qPCR). Additionally, the expression of SEC14L2 was further analyzed using The Cancer Genome Atlas-Head Neck Squamous Cell Carcinoma (TCGA-HNSCC) dataset to identify its relationship with HNSCC clinical characteristics. The Kaplan-Meier plot was used to assess survival rates, and the Tumor Immune Estimation Resource (TIMER) database was used to examine the correlation between SEC14L2 expression and tumor immune cell infiltration. In silico tools also looked at SEC14L2 involvement in cancer pathways through its protein network. The mRNA and protein levels of SEC14L2 are notably higher in both OSCC and HNSCC tissues compared to adjacent normal tissues. Upregulation of SEC14L2 was associated with advanced tumor stages, grades, metastasis, HPV-negative, and TP53 mutations in cancer patients. In addition, the high expression of SEC14L2 was negatively correlated with the poor survival of cancer patients and the infiltration of diverse immune cells in cancer patients. According to the findings of this investigation, SEC14L2 is significantly elevated in OSCC/HNSCC patients and associated with a worse prognosis. More investigation and clinical studies are required to completely understand the therapeutic potential of SEC14L2 in HNSCC and convert these findings into better patient outcomes.

High expression of novel biomarker TBRG4 promotes the progression and invasion of oral squamous cell carcinoma.

BACKGROUND: Transforming growth factor ß regulator 4 (TBRG4) is a potential prognostic indicator in various cancers, especially squamous cell carcinomas, and is associated with disease amelioration and poor outcomes. The study aimed to assess the expression pattern of TBRG4 in patients with operable oral squamous cell carcinoma (OSCC) to understand its role in tumour progression using indicators of disease outcome like tumour stage, grade, nodal metastasis, and pattern of invasion. METHODS: TBRG4 expression was assessed by analyzing 51 cancer and adjacent non-cancerous tissues of OSCC patients using quantitative real-time PCR, and Western blot. TBRG4 expression was also analysed in The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset using the UALCAN tool (http://ualcan.path.uab.edu/). The relationship between TBRG4 expression and the patient's prognosis was analysed using Kaplan-Meier plotter. RESULTS: Both mRNA and protein levels of TBRG4 were significantly increased in OSCC tissues. The TBGR4 expression was significantly associated with advanced stages (III and IV) and the worst pattern of invasion (WPOI-4 and 5). High TBRG4 expression was also significantly associated with reduced overall survival (p = 0.011). In addition, the analysis of TBRG4 gene expression and clinical data from TCGA, identified that TBRG4 was highly expressed in HPV negative OSCC patients and positively correlated with worst overall survival. CONCLUSION: The present study suggests that the high expression of TBRG4 might serve as a novel prognostic biomarker for HPV-negative OSCC, which can be validated by future additional investigations in larger cohorts along with functional studies.

RFC3 serves as a novel prognostic biomarker and target for head and neck squamous cell carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer that originates from the squamous cells. The role of the replication factor C subunit 3 (RFC3) in HNSCC progression remains elusive. The aim of this study was to uncover RFC3 significance in HNSCC. METHODS: The Cancer Genome Atlas (TCGA-HNSCC) dataset was initially used to assess RFC3 expression and its association with HNSCC clinical features. Subsequently, quantitative reverse transcription PCR (RT-qPCR) confirmed RFC3 mRNA expression in oral squamous cell carcinoma (OSCC), a primary HNSCC type. Survival rates were evaluated using the Kaplan-Meier plot, while the Tumor Immune Estimation Resource (TIMER) database probed RFC3-immune cell interaction. Additionally, in silico tools were used to examine the RFC3 protein network and engagement in HNSCC pathways. RESULTS: RFC3 expression is significantly upregulated in HNSCC, including OSCC. Upregulated RFC3 expression was significantly correlated with the clinicopathological features of HNSCC, including tumor stage, grade, metastasis, and patient survival. RFC3 is also associated with immune cell infiltration. Functional analysis has highlighted its involvement in DNA replication, mismatch repair, and cell cycle pathways. Interestingly, RFC3 high expression is linked to well-known oncogenic signaling pathways, such as MYC/MYCN, HIPPO, and mTOR. CONCLUSIONS: In conclusion, RFC3 can be considered a novel prognostic biomarker for HNSCC, and further studies on its functional mechanisms may help to use RFC3 as a therapeutic target for HNSCC. CLINICAL RELEVANCE: The clinical relevance of this study lies in identifying RFC3 as a novel biomarker and prognostic indicator for HNSCC, offering insights that could impact future clinical approaches.

Alteration in PNMA1 expression is associated with poor prognosis and tumor immune infiltration in head and neck squamous cell carcinoma.

Background: A significant percentage of the world is distressed due to the widespread and aggressive head and neck squamous cell carcinoma (HNSCC). The prognosis for people with HNSCC remains grim, despite progress in treatment techniques. This underscores the pressing demand for the discovery of novel biomarkers to enable early detection and improve prognostic categorization. Objective: The present study aims to identify the expression of the PNMA1 gene in HNSCC with clinicopathological characteristics, prognosis, and association of immune cells infiltration. Methods: The TCGA-HNSCC dataset first evaluated PNMA1 expression and its relationship to clinical aspects of HNSCC. Following that, oral squamous cell carcinoma (OSCC), a primary HNSCC type, is used to validate PNMA1 mRNA expression, via quantitative reverse transcription PCR (RT-qPCR). The Kaplan-Meier plot was used to assess survival rates, and the Tumour Immune Estimation Resource (TIMER) database was used to examine the relationship between PNMA1 and immune cells infiltration. Results: The expression of PNMA1 significantly increased in HNSCC and OSCC tumors. Significant correlations have been found between the increased PNMA1 expression and clinicopathological characteristics of HNSCC, such as tumor stage, grade, metastasis, HPV status and patient survival. PNMA1 expression also correlated with immune cell infiltration and immune regulator genes. Conclusion: In conclusion, the present study demonstrated that the PNMA1 expression significantly increased in HNSCC and was associated with HNSCC patient's prognosis. Hence, PNMA1 could serve as a novel prognostic biomarker and a promising therapeutic target for HNSCC.

Triggering receptor expressed in myeloid cells 1 (TREM1) as a potential prognostic biomarker and association with immune infiltration in oral squamous cell carcinoma.

OBJECTIVE: The objective of this study is to investigate the significance and impact of Triggering Receptor Expression on Myeloid Cells-1 (TREM-1) in the context of oral squamous cell carcinoma (OSCC). METHODS: This study involved 51 OSCC patients, 21 oral epithelial dysplasia patients (OED), and the TCGA-HNSCC dataset. TREM1 expression was analyzed using quantitative reverse transcription PCR (RT-qPCR), and Western blot. Furthermore, we assessed TREM1 expression for clinicopathological, prognosis, and immune infiltration correlations utilizing publicly available TCGA-HNSCC datasets through UALCAN, Protein Atlas, Kaplan-Meier plot, TIMER2.0, and TISIDB. We also conducted bioinformatic analyses for functional enrichment employing publicly accessible datasets. RESULTS: TREM1 was significantly upregulated in OSCC and OED when compared to normal tissues, confirmed through multiple methods. Analysis of clinicopathological features showed associations with disease stage, grade, nodal metastasis, HPV status, and TP53 mutation. High TREM1 expression correlated with poorer patient survival. TREM1 was linked to immune cell infiltration and immune-related pathways. CONCLUSION: TREM1 is significantly upregulated in OSCC and is associated with poor clinicopathological features and survival. It may hold promise as a therapeutic target and prognostic marker in OSCC. Further research is needed to understand its functional role in OSCC.

Alteration of SERPINH1 is associated with elevated expression in head and neck squamous cell carcinomas and its clinicopathological significance.

BACKGROUND/PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer-related death worldwide and contributes significantly to the burden of disease in South Asia, partially due to the lack of effective screening strategies. Identifying essential biomarkers is crucial for improved prognosis and treatment. This study investigates the potential of SERPINH1 as a prognostic marker in HNSCC, highlighting its significance amidst the molecular complexity. METHODS: The Cancer Genome Atlas HNSCC cohort, comprised of 520 tumors and 44 normal tissues, was analyzed using cBioportal, UALCAN, and Protein atlas tools. Expression patterns, survival outcomes, and clinical correlations of SERPINH1 were evaluated. In-depth analyses involved oral squamous cell carcinoma (OSCC) patient samples, protein expression, and functional exploration using various in-silico tools. RESULTS: SERPINH1 exhibited significant alteration and upregulation in HNSCC and OSCC, indicating its pan-cancer potential. Immunohistochemistry confirmed its overexpression in primary HNSCC tumors. Association analyses linked altered SERPINH1 levels with tumor stage, grade, metastasis, human papillomavirus (HPV) status, and patient prognosis. Functional analyses unveiled SERPINH1's involvement in critical cellular pathways and interactions with various proteins. CONCLUSION: The significant alteration of SERPINH1 associated with upregulated expression in HNSCC and OSCC positions it as a promising diagnostic and prognostic marker. Further investigations are warranted to elucidate the underlying molecular mechanisms, paving the way for targeted therapeutic interventions and continued exploration of various malignancies.

Overexpression of insulin-like growth factor-2 mRNA-binding protein 1 is associated with periodontal disease.

Objective: To investigate the potential role of a novel m6A RNA regulator, Insulin-like Growth Factor-2 mRNA-binding protein 1 (IGF2BP1), in periodontal disease pathogenesis. Materials and methods: Gingival tissue samples from 60 periodontitis patients and 60 healthy individuals were analyzed for IGF2BP1 mRNA and protein expression via real-time quantitative PCR (RT-qPCR) and Western blotting. Additionally, Porphyromonas gingivalis Lipopolysaccharide (Pg-LPS) -induced human gingival fibroblasts (HGFs) were evaluated for IGF2BP1 and proinflammatory cytokine expression. In silico functional analysis further explored potential molecular mechanisms. Results: IGF2BP1 mRNA and protein levels were significantly higher in the periodontitis group compared to the healthy group. Functional analysis implicated IGF2BP1 in regulating the IL-17 signaling pathway, a key player in inflammation. Pg-LPS treatment upregulated IGF2BP1 and proinflammatory cytokines in HGFs, supporting this finding. Conclusion: Our study suggests that IGF2BP1 overexpression contributes to periodontitis pathogenesis, potentially through IL-17 signaling. Further research is needed to elucidate the precise molecular mechanisms and explore IGF2BP1 as a potential therapeutic target or biomarker for this common oral disease.

Triggering Receptor Expression on Myeloid Cells-1 (TREM1) Promoter Hypomethylation and Its Overexpression Associated With Poor Survival of Cancer Patients: A Pan-Cancer Analysis.

Background Triggering receptor expression on myeloid cells-1 (TREM1) belongs to the immunoglobulin superfamily and is implicated in various conditions, including infectious and non-infectious diseases, autoimmune disorders, and cancer. Notably, TREM1 is significantly dysregulated in numerous cancer types. However, the underlying mechanism driving TREM1 mRNA expression in cancers remains unclear.  Objective This study aims to analyze the promoter methylation level of TREM1 and its overexpression with cancer. Methods  This study utilized The Cancer Genome Atlas (TCGA) cohort to analyze the methylation and expression levels of TREM1 in cancers. The University of ALabama at Birmingham CANcer (UALCAN) database facilitated data analysis from the TCGA dataset. Additionally, survival analysis was conducted using the TCGA dataset via Kaplan-Meier (KM) plots to identify significant associations with prognosis. Results Promoter methylation analysis revealed that TREM1 is hypomethylated in cancers, resulting in significantly overexpressed mRNA across various cancer types. This methylation and expression showed a negative correlation. Furthermore, high TREM1 mRNA expression was linked to poor prognosis in several cancers. Conclusion TREM1 gene expression negatively correlates with promotor DNA methylation and is associated with poor survival. It may serve as a prognostic marker and biomarker for various cancers. Future research should focus on further validation and antitumor immunity to elucidate its oncogenic role in cancers.

Dysregulation of a novel m6A regulator YWHAG is correlated with metastasis and poor prognosis in oral squamous cell carcinoma - A cross-sectional study.

OBJECTIVE: This study aimed to investigate the role of a novel m6A and cell cycle regulator YWHAG in oral squamous cell carcinoma (OSCC) by analyzing its expression and functional implications. DESIGN: Tumor samples (n = 51) and adjacent non-tumor samples (n = 38) were collected from patients with OSCC, and cell lines were processed. YWHAG mRNA expression was assessed using quantitative reverse transcription PCR (RT-qPCR) analysis. Various tools, such as UALCAN, Protein-Atlas analysis, TIMER 2.0, and other in silico tools, were used to explore clinicopathological correlations, protein expression, immune cell infiltration, and functional associations of YWHAG. RESULTS: YWHAG mRNA and protein expression were significantly upregulated in OSCC tumor tissues and OSCC cell lines compared to non-tumor tissues and normal cells (p < 0.001). High YWHAG expression significantly correlated with advanced tumor stage, higher grade, lymph node metastasis, and poor prognosis (p < 0.05). Functional analysis revealed that YWHAG is associated with pathways involved in aggressive cancer progression. YWHAG expression positively correlated with its target gene CTTN expression, which was also upregulated in OSCC and associated with poor prognosis (p < 0.05). CONCLUSIONS: Study findings indicate that YWHAG may contribute to the progression of OSCC and could be a potential therapeutic target or prognostic biomarker. Further investigation is necessary to understand the underlying mechanisms and assess the clinical implications of YWHAG dysregulation in OSCC.

Aberrant expression of VASP serves as a potential prognostic biomarker and therapeutic target for oral squamous cell carcinoma.

OBJECTIVE: To address the molecular markers linked to the development and progression of oral squamous cell carcinoma (OSCC), we sought to analyze the expression of vasodilator-stimulated phosphoproteins (VASP) in OSCC samples. STUDY DESIGN: This study used 51 OSCC patients and The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset to analyze VASP expression. The association between VASP mRNA expression and HNSCC clinicopathological features, tumor infiltration, functional roles, and gene co-expression of VASP also were evaluated. RESULTS: Our study observed increased VASP mRNA expression in OSCC tumor tissues compared to normal tissues, supported by TCGA-HNSC dataset analysis. Elevated VASP levels correlated with advanced tumor stage, higher grade, nodal metastasis, and poor survival, indicating its potential as a prognostic marker. Protein analysis and immunohistochemistry confirmed these findings, and in silico analysis revealed VASP involvement in key cancer-related processes and its correlation with IL8, RAP1A expression, and tumor infiltration levels. CONCLUSIONS: In conclusion, VASP emerges as a promising diagnostic and prognostic marker for OSCC within HNSCC, emphasizing the importance of exploring its regulatory mechanisms and therapeutic applications. The revealed pathways present avenues for targeted treatment in OSCC. Despite limitations, this study provides valuable insights with potential implications for improving patient outcomes.

EXT2: a novel prognostic and predictive biomarker for head and neck squamous cell carcinoma.

OBJECTIVE: This study focused on EXT2, a member of the EXT family involved in heparan sulfate synthesis, to evaluate its potential as a prognostic and predictive biomarker in head-neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The present study used the cancer genome atlas head-neck squamous cell carcinoma (TCGA-HNSC) dataset-based UALCAN database to analyze the EXT2 expression and its clinicopathological features. In addition, we recruited 51 oral squamous cell carcinoma patients (OSCC), the most common HNSCC subtype, to validate the EXT2 mRNA expression analysis. In addition, we identified the role of EXT2 in prognosis using a Kaplan-Meier plot and immune signature using the tumor infiltration level. Furthermore, functional roles were analyzed using the EXT2 gene and protein networks. RESULTS: The expression of EXT2 mRNA was significantly upregulated in OSCC tumors, which is consistent with the UALCAN-based results. EXT2 protein was also significantly overexpressed in HNSCC samples and was correlated with clinicopathological features. High EXT2 expression is associated with poor survival outcomes in HNSCC patients. Functional analysis of EXT2 using in silico tools revealed its involvement in critical pathways, including Wnt signaling, proteoglycans in cancer, and cellular responses to fibroblast growth and inflammation. CONCLUSION: These findings highlight the potential of EXT2 as a prognostic and predictive biomarker of HNSCC.

Waterpipe smoke condensate induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by FOXD1 expression.

BACKGROUND/PURPOSE: Smoking is a major contributor to global oral cancer cases, necessitating urgent intervention. FOXD1, involved in developmental processes and various cancers, shows promise as a prognostic marker in oral squamous cell carcinoma (OSCC). This study investigates the impact of waterpipe smoke condensate (WPSC) on OSCC, focusing on FOXD1 role in inducing epithelial-mesenchymal transition (EMT) and metastasis. METHODS: The study involved using OSCC cells treated with WPSC to evaluate their proliferation, colony formation, gene expression, and protein levels. The researchers also explored the clinical relevance of their findings using online databases to analyze FOXD1 expression in cancer tissues and its correlation with clinicopathological features and patient survival. Additionally, in silico tools were employed for functional analysis, pathway enrichment, and network exploration. RESULTS: The study found that WPSC increased the expression of FOXD1 in OSCC cells, which led to increased cell growth. The study also showed that FOXD1 plays a critical role in the EMT process induced by WPSC, as evidenced by changes in the expression of EMT-related genes and proteins. Clinical analysis revealed that FOXD1 was significantly associated with more aggressive tumor features and poorer prognosis in cancer patients. CONCLUSION: The study highlights FOXD1 as a key player in OSCC pathogenesis and a potential prognostic marker and therapeutic target, particularly when influenced by WPSC exposure. Further research is needed to explore FOXD1 molecular mechanisms and clinical implications to enhance OSCC treatment strategies.

The implication of mitochondrial DNA mutation and dysfunction in periodontal diseases.

Periodontitis is a chronic oral inflammatory disease that is caused by dental plaque pathogens. Periodontal disease development and evolution are based on the host immune system, humoral and cellular immunity, the integrity of the tissues, and certain endocrine and nutritional factors. Mitochondria are significantly involved in periodontal infections and inflammation, which play a role in the inflammatory response in a variety of ways. In general, oxidative stress causes a stressful environment that subsequently leads to tissue damage and chronic inflammation. Several mutations and alterations in mitochondrial DNA lead the disease to an aggressive condition, by causing dysregulated mitochondrial function. Such mutations are significantly associated with various diseases. Numerous studies indicate chronic periodontitis patients have a decreased level of mitochondrial membrane potential, as well as adenosine triphosphate, and an increased level of reactive oxygen species production, which causes cell death in the periodontium and affects tissue growth. Further studies into the association between mitochondria and periodontitis might be helpful for the treatment and prevention of the diseases.

Prognostic and clinicopathological significance of MRC2 expression in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive types of cancers worldwide, with metastasis being the major cause of death. Recent research suggests that changes in the expression of MRC2 (mannose receptor, C-type 2) may play a role in the development and progression of various cancers; however, its expression pattern in HNSCC/ OSCC is unknown. This study aimed to elucidate the clinicopathological significance and prognostic role of MRC2 expression in HNSCC, including OSCC. MATERIALS AND METHODS: In the present study, we assessed the potential roles of MRC2 in expression, prognostic value, immune infiltration and functional enrichment analysis in HNSCC patients by using different bioinformatics databases. We then validated MRC2 gene expression in 30 OSCC and adjacent normal tissue samples using quantitative reverse transcription PCR (RT-qPCR). RESULTS: MRC2 mRNA and protein expression were significantly upregulated in OSCC and HNSCC patients compared to that in adjacent normal tissues. Upregulated MRC2 expression was associated with poor overall survival. Increased MRC2 expression has also been linked to an aggressive clinicopathological features including advanced stages, grade, metastasis and HPV status. Interestingly, our in silico results strongly suggest that the MRC2 gene and protein interaction networks are associated with HNSCC development. Moreover, the tumor infiltration level was significantly correlated with HPV-negative HNSCC patients. CONCLUSION: Our results suggest that MRC2 could be used as a novel prognostic marker and therapeutic target for HNSCC.

Decreased expression of the m6A RNA methyltransferase METTL3 is associated with residual ridge resorption.

Objective: N6-methyladenosine (m6A) methylation and its regulators play crucial roles in the progression of osteoporosis (OP) by regulating the expression of osteoporosis-related genes. In this study, we have analyzed the expression of methyltransferase-like 3 (METTL3) and its target gene Runt-related transcription factor 2 (RUNX2) in patients with residual ridge resorption (RRR). Materials and methods: A total 50 number of participants were included in this comparative study (RRR - n25 and healthy control - n25). Total RNA was extracted from peripheral blood and converted into cDNA. METTL3 and RUNX2 expression levels were quantified using RT-qPCR with GAPDH as the reference gene. Bioinformatics tools were used to identify gene functions and pathways. Results: Real-time polymerase chain reaction (qPCR) revealed that METTL3 and RUNX2 expression was downregulated in the RRR group compared to that in healthy controls (P < 0.05). In silico functional analysis provided information regarding the role of METTL3 in various biological processes. Conclusion: Our findings suggest that METTL3 dysregulation contributes to RRR pathogenesis. Further large-scale samples and functional studies are required to identify their therapeutic potential.

A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype-Phenotype Analysis.

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the BTD gene are reported worldwide. Mutations in the BTD gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the BTD gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.