Lymphopenia associated with survivin and its downstream pathway in COVID-19 serving as a potential route in COVID-19 pathogenesis.

PURPOSE: Starting in 2019, coronavirus disease 2019 (COVID-19) caused an epidemic that was growing rapidly and has harmed millions of people globally. It has been demonstrated that survivin regulates lymphocyte survival, a main route involved in COVID-19 pathogenesis. Survivin belongs to the inhibitor of apoptosis protein (IAP) family, and its primary functions comprise regulating mitosis and inhibiting apoptosis. Since lower survivin expression has been shown to increase the sensitivity of lymphocytes to apoptotic induction, we looked into the function of survivin and its corresponding pathways in COVID-19 pathogenesis. MATERIALS AND METHODS: The expression of survivin, X-linked inhibitor of apoptosis protein (XIAP), caspases 3, 7, 9, and poly (ADP-ribose) polymerase (PARP) was evaluated at both mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with severe and moderate COVID-19 by qRT-PCR and Western blotting, respectively. Then, we enforced apoptosis to COVID-19 patient-derived lymphocytes, and the percent was assessed by flow cytometry. RESULTS: Survivin and XIAP were less expressed in PBMCs derived from COVID-19 patients as apoptosis inhibitors than PARP, cleaved-PARP, caspase 9, and cleaved caspases 3 and 7, according to the results of real-time PCR and Western blot analysis. Additionally, according to the flow cytometry results, the down-regulation of survivin served as a potential factor in the lymphocyte depletion observed in patients with COVID-19. CONCLUSION: The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.

Thymoquinone potentiates anti-cancer effects of cisplatin in oral squamous cell carcinoma via targeting oxidative stress.

Recent evidence has proved that thymoquinone as a natural polyphenol has great anticancer and anti-proliferative effects in cancer cells. In this study, we aimed to examine the effects of thymoquinone on increasing cisplatin-induced apoptosis human oral squamous cell carcinoma cells and its underlying molecular mechanisms. SCC-25 cancer cells treated by thymoquinone and cisplatin with different concentrations. Cell viability will determine by using MTT assay. The concentrations of reactive oxygen species (ROS) and antioxidant activities were determined using specific related kits. DNA damage, lipid, and protein oxidation were assessed. Real-time PCR and Western blot analysis will be used to determine the expression of apoptosis-related proteins including Bax, Bcl-2, and caspase-3. Combination of thymoquinone and cisplatin suppressed synergistically SCC-25 cancer cell viability and induced apoptosis in dose-depended manner. Cell treatment with combination of thymoquinone and cisplatin led to accumulation of ROS within cells and increase in the intracellular levels of DNA damage, protein and lipid peroxidation. In addition, the combination of thymoquinone and cisplatin modulated the mRNA and protein expression levels of apoptosis-related proteins including Bax, Bcl-2, and caspase-3. Thymoquinone potentiated cisplatin anti-cancer effect on OSCC by inducing oxidative stress in cells.

Mesenchymal Stem Cell-based Scaffolds in Regenerative Medicine of Dental Diseases.

Biomedical engineering breakthroughs and increased patient expectations and requests for more comprehensive care are propelling the field of regenerative dentistry forward at a fast pace. Stem cells (SCs), bioactive compounds, and scaffolds are the mainstays of tissue engineering, the backbone of regenerative dentistry. Repairing damaged teeth and gums is a significant scientific problem at present. Novel therapeutic approaches for tooth and periodontal healing have been inspired by tissue engineering based on mesenchymal stem cells (MSCs). Furthermore, as a component of the MSC secretome, extracellular vesicles (EVs) have been shown to contribute to periodontal tissue repair and regeneration. The scaffold, made of an artificial extracellular matrix (ECM), acts as a supporting structure for new cell development and tissue formation. To effectively promote cell development, a scaffold must be non-toxic, biodegradable, biologically compatible, low in immunogenicity, and safe. Due to its promising biological characteristics for cell regeneration, dental tissue engineering has recently received much attention for its use of natural or synthetic polymer scaffolds with excellent mechanical properties, such as small pore size and a high surface-to-volume ratio, as a matrix. Moreover, as a bioactive material for carrying MSC-EVs, the combined application of scaffolds and MSC-EVs has a better regenerative effect on dental diseases. In this paper, we discuss how MSCs and MSC-derived EV treatment may be used to regenerate damaged teeth, and we highlight the role of various scaffolds in this process.

Spotlight on therapeutic efficiency of green synthesis metals and their oxide nanoparticles in periodontitis.

Periodontitis, one of the most prevalent dental diseases, causes the loss of bone and gum tissue that hold teeth in place. Several bacteria, commonly present in clinically healthy oral cavities, may induce and perpetuate periodontitis when their concentration rises in the gingival sulcus. Antibacterial effect against various Gram-negative and Gram-positive bacteria, including pathogenic and drug-resistant ones, has been shown for several distinct transient metal and metal oxide NPs. Therefore, NPs may be used in biomedicine to treat periodontal problems and in nanotechnology to inhibit the development of microorganisms. Instead of using harmful chemicals or energy-intensive machinery, biosynthesis of metal and metal oxide nanoparticles (NPs) has been suggested. To produce metal and metal oxide NPs, the ideal technique is "Green" synthesis because of its low toxicity and safety for human health and the environment. Gold NPs (AuNPs) appear to be less toxic to mammalian cells than other nanometals because their antibacterial activity is not dependent on reactive oxygen species (ROS). AgNPs also possess chemical stability, catalytic activity, and superior electrical and thermal conductivity, to name a few of their other advantageous characteristics. It was observed that zinc oxide (ZnO) NPs and copper (Cu) NPs exhibited discernible inhibitory effects against gram-positive and gram-negative bacterial strains, respectively. ZnO NPs demonstrated bactericidal activity against the microorganisms responsible for periodontitis. Medications containing magnetic NPs are highly effective against multidrug-resistant bacterial and fungal infections. The titanium dioxide (TiO2) NPs are implicated in elevating salivary peroxidase activity in individuals diagnosed with chronic periodontitis. Furthermore, specific metallic NPs have the potential to enhance the antimicrobial efficacy of periodontitis treatments when combined. Therefore, these NPs, as well as their oxide NPs, are only some of the metals and metal oxides that have been synthesized in environmentally friendly ways and shown to have therapeutic benefits against periodontitis.

Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.

Oral squamous cell carcinoma (OSCC) is a prevalent and significant type of oral cancer that has far-reaching health implications worldwide. Epigenetics, a field focused on studying heritable changes in gene expression without modifying DNA sequence, plays a pivotal role in OSCC. Epigenetic changes, encompassing DNA methylation, histone modifications, and miRNAs, exert control over gene activity and cellular characteristics. In OSCC, aberrant DNA methylation of tumor suppressor genes (TSG) leads to their inactivation, subsequently facilitating tumor growth. As a result, distinct patterns of gene methylation hold promise as valuable biomarkers for the detection of OSCC. Oral cancer treatment typically involves surgery, radiation therapy, and chemotherapy, but even with these treatments, cancer cells cannot be effectively targeted and destroyed. Researchers are therefore exploring new methods to target and eliminate cancer cells. One promising approach is the use of epigenetic modifiers, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, which have been shown to modify abnormal epigenetic patterns in OSCC cells, leading to the reactivation of TSGs and the suppression of oncogenes. As a result, epigenetic-targeted therapies have the potential to directly alter gene expression and minimize side effects. Several studies have explored the efficacy of such therapies in the treatment of OSCC. Although studies have investigated the efficacy of epigenetic therapies, challenges in identifying reliable biomarkers and developing effective combination treatments are acknowledged. Of note, epigenetic mechanisms play a significant role in drug resistance in OSCC and other cancers. Aberrant DNA methylation can silence tumor suppressor genes, while alterations in histone modifications and chromatin remodeling affect gene expression related to drug metabolism and cell survival. Thus, understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve the efficacy of cancer treatments in OSCC. This comprehensive review focuses on the complex interplay between epigenetic alterations and OSCC cells. This will involve a deep dive into the mechanisms underlying epigenetic modifications and their impact on OSCC, including its initiation, progression, and metastasis. Furthermore, this review will present the role of epigenetics in the treatment and diagnosis of OSCC.

Study of Cytotoxic and Antibacterial Activity of Ag- and Mg-Dual-Doped ZnO Nanoparticles.

A non-laborious process for the fabrication of silver and magnesium dual doped zinc oxide nanoparticles (Ag/Mg-ZnO NP) is described. The wurtzite ZnO nano-structures and the dual doped NP were analyzed by PXRD. SEM data showed the hexagonal morphology of our product, while the gathered anti-bacterial outcomes towards Streptococcus mutans bacteria through micro-dilution technic affirmed the enhanced performance of doped NP compared to the native ones. Furthermore, we gauged the toxic impacts of synthesized pure and Ag/Mg-ZnO NP against a breast cancer (MDA-MB-231) cell line through an MTT trial, which highlighted the superiority of the doped when compared to the native nanoparticles. In light of these comparisons, the applicability of Ag/Mg-ZnO NP in dental and medical science is proposed.

Gingival mesenchymal stem cell therapy, immune cells, and immunoinflammatory application.

MSC-based therapeutic strategies have proven to be incredibly effective. Robust self-renewal, multilineage differentiation, and potential for tissue regeneration and disease treatments are all features of MSCs isolated from oral tissue. Human exfoliated deciduous teeth, dental follicles, dental pulp, apical papilla SCs, and alveolar bone are the primary sources of oral MSC production. The early immunoinflammatory response is the first stage of the healing process. Oral MSCs can interact with various cells, such as immune cells, revealing potential immunomodulatory regulators. They also have strong differentiation and regeneration potential. Therefore, a ground-breaking strategy would be to research novel immunomodulatory approaches for treating disease and tissue regeneration that depend on the immunomodulatory activities of oral MSCs during tissue regeneration.

Periodontitis and progression of gastrointestinal cancer: current knowledge and future perspective

Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis (AU)

MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases.

Undifferentiated, highly proliferative, clonogenic, and self-renewing dental stem cells have paved the way for novel approaches to mending cleft palates, rebuilding lost jawbone and periodontal tissue, and, most significantly, recreating lost teeth. New treatment techniques may be guided by a better understanding of these cells and their potential in terms of the specificity of the regenerative response. MicroRNAs have been recognized as an essential component in stem cell biology due to their role as epigenetic regulators of the processes that determine stem cell destiny. MicroRNAs have been proven to be crucial in a wide variety of molecular and biological processes, including apoptosis, cell proliferation, migration, and necrocytosis. MicroRNAs have been recognized to control protein translation, messenger RNA stability, and transcription and have been reported to play essential roles in dental stem cell biology, including the differentiation of dental stem cells, the immunological response, apoptosis, and the inflammation of the dental pulp. Because microRNAs increase dental stem cell differentiation, they may be used in regenerative medicine to either preserve the stem cell phenotype or to aid in the development of tooth tissue. The development of novel biomarkers and therapies for dental illnesses relies heavily on progress made in our knowledge of the roles played by microRNAs in regulating dental stem cells. In this article, we discuss how dental stem cells and their associated microRNAs may be used to cure dental illness.

Oral manifestations of COVID-19 and its management in pediatric patients: A systematic review and practical guideline.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes coronavirus disease 2019 (COVID-19), a respiratory infection that has spread worldwide and is responsible for a high death toll. Although respiratory symptoms are the most common, there is growing evidence that oral signs of COVID-19 can also be seen in children. The purpose of this systematic review is to provide a comprehensive analysis of the available data on the oral manifestations of COVID-19 in children and to recommend appropriate methods of diagnosis and treatment. METHODS: A systematic search of the MEDLINE, EMBASE, Scopus, and Web of Science databases was done to discover relevant papers published between their establishment and January 2023. Articles detailing oral symptoms in pediatric patients with confirmed COVID-19 infection were included, and data on clinical characteristics, diagnosis, treatment, and outcomes were extracted and evaluated. RESULTS: A total of 24 studies involving 2112 pediatric patients with COVID-19 were included in the review. The most common presentations are oral lesions, taste and smell disorders, oral candidiasis, hemorrhagic crust, tongue discoloration, lip and tongue fissuring, gingivitis, and salivary gland inflammation. These manifestations were sometimes associated with multi-system inflammatory syndrome in children (MIS-C) or Kawasaki disease (KD). Management strategies varied depending on the severity of the oral manifestation and ranged from symptomatic relief with topical analgesics to systemic medications. CONCLUSION: Oral symptoms of COVID-19 are relatively prevalent in juvenile patients and can be accompanied by severe systemic diseases, such as MIS-C or Kawasaki illness. Early detection and adequate care of these oral symptoms are critical for the best patient results. Understanding the underlying pathophysiology and developing targeted treatments requires more investigation.

Recent advances in metal nanoparticles to treat periodontitis.

The gradual deterioration of the supporting periodontal tissues caused by periodontitis, a chronic multifactorial inflammatory disease, is thought to be triggered by the colonization of dysbiotic plaque biofilms in a vulnerable host. One of the most prevalent dental conditions in the world, periodontitis is now the leading factor in adult tooth loss. When periodontitis does develop, it is treated by scraping the mineralized deposits and dental biofilm off the tooth surfaces. Numerous studies have shown that non-surgical treatment significantly improves clinical and microbiological indices in individuals with periodontitis. Although periodontal parameters have significantly improved, certain bacterial reservoirs often persist on root surfaces even after standard periodontal therapy. Periodontitis has been treated with local or systemic antibiotics as well as scaling and root planning. Since there aren't many brand-new antibiotics on the market, several researchers are currently concentrating on creating alternate methods of combating periodontal germs. There is a delay in a study on the subject of nanoparticle (NP) toxicity, which is especially concerned with mechanisms of action, while the area of nanomedicine develops. The most promising of them are metal NPs since they have potent antibacterial action. Metal NPs may be employed as efficient growth inhibitors in a variety of bacteria, making them useful for the treatment of periodontitis. In this way, the new metal NPs contributed significantly to the development of efficient anti-inflammatory and antibacterial platforms for the treatment of periodontitis. The current therapeutic effects of several metallic NPs on periodontitis are summarized in this study. This data might be used to develop NP-based therapeutic alternatives for the treatment of periodontal infections.

Spotlight on the impact of viral infections on Hematopoietic Stem Cells (HSCs) with a focus on COVID-19 effects.

Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc. Video Abstract.

Periodontitis and progression of gastrointestinal cancer: current knowledge and future perspective.

Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.

MiR-34 by targeting p53 induces apoptosis and DNA damage in paclitaxel-resistant human oral squamous carcinoma cells.

MicroRNA-34 (miR-34) is one the most important tumor suppressor miRNAs involving in the various aspects of oral cancer. The present study aimed to evaluate the effects of miR-34 restoration in OECM-1 oral cancer resistant to paclitaxel (OECM-1/PTX) and its underlying mechanisms through p53-mediated DNA damage and apoptosis. OECM-1 and OECM-1/PTX were transfected with miR-34 mimic and inhibitor. Cellular proliferation and apoptosis were evaluated through MTT assay and flow cytometry, respectively. The mRNA and protein expression levels of p53, p-glycoprotein (P-gp), ATM, ATR, CHK1, and CHK2 were assessed through qRT-PCR and western blotting. Rhodamin123 uptake assay was used to measure the P-gp activities. P53 expression was also suppressed by sing a siRNA transfection of cells. The expression levels of miR-34 were downregulated in OECM-1/PTX. Restoration of miR-34 led to increase in cytotoxic effects of paclitaxel in cells. In addition, the expression levels and activities of P-gp were reduced following miR-34 transfection. miR-34 transfection upregulated the p53, ATM, ATR, CHK1, and CHK2 expression levels in OECM-1/PTX cells. Furthermore, cells transfected with miR-34 showed higher levels of apoptosis. miR-34 restoration reverses paclitaxel resistance in OECM-1 oral cancer. The chemosensitive effects of miR-34 is mediated through increasing DNA damage and apoptosis in a p53 depended manner.