Oral microbiota and oral squamous cell carcinoma: a review of their relation and carcinogenic mechanisms.

Oral Squamous Cell Carcinoma (OSCC) is the most common type of head and neck cancer worldwide. Emerging research suggests a strong association between OSCC and the oral microbiota, a diverse community of bacteria, fungi, viruses, and archaea. Pathogenic bacteria, in particular Porphyromonas gingivalis and Fusobacterium nucleatum, have been closely linked to OSCC. Moreover, certain oral fungi, such as Candida albicans, and viruses, like the human papillomavirus, have also been implicated in OSCC. Despite these findings, the precise mechanisms through which the oral microbiota influences OSCC development remain unclear and necessitate further research. This paper provides a comprehensive overview of the oral microbiota and its relationship with OSCC and discusses potential carcinogenic pathways that the oral microbiota may activate or modulate are also discussed.

Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms.

BACKGROUND: Gemfibrozil (Gem) is a drug that has been shown to activate PPAR-α, a nuclear receptor that plays a key role in regulating lipid metabolism. Gem is used to lower the levels of triglycerides and reduce the risk of coronary heart disease in patients. Experimental studies in vitro and in vivo have shown that Gem can prevent or slow the progression of neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation is known to play a significant role in these disorders. METHOD: The literature review for this study was conducted by searching Scopus, Science Direct, PubMed, and Google Scholar databases. RESULT: The results of this study show that Gem has neuroprotective effects through several cellular and molecular mechanisms such as: (1) Gem has the ability to upregulate pro-survival factors (PGC-1α and TFAM), promoting the survival and function of mitochondria in the brain, (2) Gem strongly inhibits the activation of NF-κB, AP-1, and C/EBPß in cytokine-stimulated astroglial cells, which are known to increase the expression of iNOS and the production of NO in response to proinflammatory cytokines, (3) Gem protects dopamine neurons in the MPTP mouse model of PD by increasing the expression of PPARα, which in turn stimulates the production of GDNF in astrocytes, (4) Gem reduces amyloid plaque pathology, reduces the activity of glial cells, and improves memory, (5) Gem increases myelin genes expression (MBP and CNPase) via PPAR-ß, and (6) Gem increases hippocampal BDNF to counteract depression. CONCLUSION: According to the study, Gem was investigated for its potential therapeutic effect in NDs. Further research is needed to fully understand the therapeutic potential of Gem in NDs.

The Anti-hypoxia Potentials of Trans-sodium Crocetinate in Hypoxiarelated Diseases: A Review.

Crocetin is a kind of apocarotenoid carboxylic acid extracted from saffron (Crocus sativus L.), which is effective in upregulating tissue oxygenation. However, crocetin is difficult to solubilize. It was shown that the trans isomer of crocetin is effective in improving oxygen diffusivity, while its cis isomer appears not to be. Hence, the isolated trans isomer of crocetin or trans-sodium crocetinate (TSC) can be used instead of crocetin. It is shown that TSC can upregulate hypoxic tissue oxygenation and be effective in treating some hypoxia-related diseases. Moreover, experimental and clinical studies have reported no adverse effects following TSC treatment, even at high doses. The current study will discuss the potential role of TSC in hemorrhagic shock, ischemia, brain tumor radiotherapy, and others.

The emerging crosstalk between atherosclerosis-related microRNAs and Bermuda triangle of foam cells: Cholesterol influx, trafficking, and efflux.

In atherosclerosis, the gradual buildup of lipid particles into the sub-endothelium of damaged arteries leads to numerous lipid alterations. The absorption of these modified lipids by monocyte-derived macrophages in the arterial wall leads to cholesterol accumulation and increases the likelihood of foam cell formation and fatty streak, which is an early characteristic of atherosclerosis. Foam cell formation is related to an imbalance in cholesterol influx, trafficking, and efflux. The formation of foam cells is heavily regulated by various mechanisms, among them, the role of epigenetic factors like microRNA alteration in the formation of foam cells has been well studied. Recent studies have focused on the potential interplay between microRNAs and foam cell formation in the pathogenesis of atherosclerosis; nevertheless, there is significant space to progress in this attractive field. This review has focused to examine the underlying processes of foam cell formation and microRNA crosstalk to provide a deep insight into therapeutic implications in atherosclerosis.

Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism.

MicroRNAs (miRNAs) are emerging as a significant modulator of immunity, and their abnormal expression/activity has been linked to numerous human disorders, such as cancer. It is now known that miRNAs potentially modulate the production of several metabolic processes in tumor-associated immune cells and indirectly via different metabolic enzymes that affect tumor-associated signaling cascades. For instance, Let-7 has been identified as a crucial modulator for the long-lasting survival of CD8+ T cells (naive phenotypes) in cancer by altering their metabolism. Furthermore, in T cells, it has been found that enhancer of zeste homolog 2 (EZH2) expression is controlled via glycolytic metabolism through miRNAs in patients with ovarian cancer. On the other hand, immunometabolism has shown us that cellular metabolic reactions and processes not only generate ATP and biosynthetic intermediates but also modulate the immune system and inflammatory processes. Based on recent studies, new and encouraging approaches to cancer involving the modification of miRNAs in immune cell metabolism are currently being investigated, providing insight into promising targets for therapeutic strategies based on the pivotal role of immunometabolism in cancer. Throughout this overview, we explore and describe the significance of miRNAs in cancer and immune cell metabolism.

Nanovaccines in cancer immunotherapy: Focusing on dendritic cell targeting.

Cancer immunotherapy is proposed to eradicate tumors by stimulating host anti-tumor immunity through utilizing various therapeutic approaches. Cancer vaccines have become a promising approach for cancer immunotherapy among the proposed platforms, either alone or in combination with other therapeutic agents. Due to the suboptimal efficacy of cancer vaccines in clinical trials and the advent of nanotechnology in the biomedicine field, scientists developed nanoplatforms, such as various nanoparticles (NPs), cell-derived components, and nanocomplexes, to deliver vaccine components to target cells and tissues, thereby supporting their anti-tumor efficacy and minimizing adverse side effects. To increase the therapeutic effects of nanovaccines in cancer therapy, dendritic cell (DC) targeting through the modulation of the structure of the vaccines, such as using DC-specific ligands, has attracted extensive interest. Here, we reviewed the various forms of nanovaccines in cancer therapy and their therapeutic effects; we highlighted the properties and functions of DCs as the main antigen-presenting cells in immune responses and focused on targeting DCs in developing nanovaccines.

Leukocyte telomere length and obesity in children and adolescents: A systematic review and meta-analysis.

Background: Several studies have revealed the negative effects of adiposity on telomere length shortening. However, the results of the studies assessing the negative relationship between obesity and leukocyte telomere length (LTL) are not consistent. This systematic review and meta-analysis are aimed to pool the results of articles assessing the relationship between obesity and LTL among children and adolescents. Methods: To retrieve the related studies, four online databases including PubMed, Embase, ProQuest, and Scopus were searched until May 2022. Observational studies evaluating the relationship between obesity and LTL among apparently healthy children and adolescents (aged ≤18 years) were included in the study. We considered the studies that had reported a mean ± standard deviation of LTL. The random-effects model was used to assess the pooled weighted mean difference (WMD) and a 95% confidence interval (CI). Results: The search yielded seven studies from an initial 3,403 records identified. According to the results of seven articles with 4,546 participants, obesity was associated with LTL shortening among children and adolescents (WMD = -0.081; 95% CI: -0.137 to -0.026; p = 0.004; I2 = 99.9%). Also, no publication bias was observed. According to the results of subgrouping, significant results were only attributed to the studies conducted in Europe, with high quality scores, among overweight and obese adolescents, with a baseline LTL lower than 1, and performed in community-based school settings. Also, according to the subgrouping and meta-regression results, the obesity definition criteria and baseline LTL were the possible sources of between-study heterogeneity. Conclusion: We observed shorter LTL among overweight and obese children and adolescents. To obtain more reliable results, further longitudinal prospective studies with large sample sizes and more consistent and accurate definitions of obesity are required.

Synthesis of Bioactive Yttrium-Metal-Organic Framework as Efficient Nanocatalyst in Synthesis of Novel Pyrazolopyranopyrimidine Derivatives and Evaluation of Anticancer Activity.

Novel Yttrium-metal-organic framework (Y-MOF) was synthesized under optimal conditions of microwave with a power of 20 W, the temperature of 30 degrees of centigrade, and time duration of 10 min. The products were characterized by SEM (morphology and size distribution), TGA (thermal stability), BET technique (surface area), and FTIR (characterization of the related group). The Yttrium-metal-organic framework (Y-MOF) synthesized in this study, after identifying and confirming the structure, was used as an efficient and recyclable catalyst in the synthesis of new pyrazolopyranopyrimidine derivatives. Following the study of the properties and applications of Y-MOF, its anticancer properties on breast cancer cells based on the MTT method were evaluated, and significant results were observed. In addition, the anticancer properties of the pyrazolopyranopyrimidine derivatives were investigated.

Hurdles to breakthrough in CAR T cell therapy of solid tumors.

Autologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising outcomes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells. Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its beneficial effect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/off-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.

Effectiveness of Combination of Chitosan Gel and Hydroxyapatite from Crabs Shells (Portunus pelagicus) Waste as Bonegraft on Periodontal Network Regeneration through IL-1 and BMP-2 Analysis.

Background: Periodontitis can be treated by regenerating periodontal tissue using a bone graft. Several natural materials such as chitosan and minerals such as hydroxyapatite can be developed to increase periodontal tissue regeneration. Chitosan has a high potential in healing wounds. Hydroxyapatite has excellent properties such as biocompatibility, osteoconductive, osteoinductive, and osteogenesis, making it an ideal material for soft and hard tissue regeneration. Chitosan and hydroxyapatite can be obtained from the shells of crustaceans, such as crabs shells (Portunus pelagicus). Objective: To assess the effectiveness of the combination of chitosan gel and hydroxyapatite powder as a bone graft on periodontal tissue regeneration in experimental animals. Periodontal tissue regeneration was assessed by expressing inflammatory cytokine gene indicators IL-1 and BMP-2. Methods: Experimental laboratory research and clinical trials with posttest only control group design. Twenty-seven Wistar rats were divided into three groups. Then the femoral bone defect was made, the positive control group was given placebo gel, the positive control group was given BATAN hydroxyapatite, and the test group was given a combination of chitosan gel and hydroxyapatite crab shells. Wistar rats were sacrificed on days 7, 14, and 21, and the femur bone was then taken for immunohistochemical analysis to determine the levels of IL-1 and BMP-2. The Kolmogorov-Smirnov test, Levene test, and one-way ANOVA analyzed the data. Results: On days 7, 14, and 21, the expression levels of IL-1 and BMP2 were significantly different between the three groups. The group added with chitosan gel and crab shell HA showed a faster decrease in IL-1 expression than the control group. BMP-2 expression increased in the test group compared to the control group. Conclusion: The combination of chitosan gel and hydroxyapatite inhibited the production of proinflammatory cytokines and increased the production of BMP-2.

Virgin Coconut Oil as a New Concept for Periodontal Tissue Regeneration via Expressions of TNF-α and TGF-ß1.

BACKGROUND: Virgin coconut oil is a natural product from coconut that has many benefits such as antibacterial, anti-inflammatory, and antioxidant. Inflammatory disease of the periodontal tissues has a high prevalence worldwide. The main etiology of periodontitis plaque of biofilm contains colonies of pathogenic microorganisms. The occurrence of inflammation in the periodontal tissue stimulates the release of inflammatory mediators, such as TNF-α and TGF-ß. Treatment for periodontitis can be performed starting from initial therapy and usually accompanied by additional therapy such as local drug delivery. VCO can be used as an alternative to antibiotics. OBJECTIVE: To determine the effectiveness of VCO gel on periodontal tissue regeneration materials through the expression of TNF-α and TGF-ß1. METHODS: This is an experimental laboratory with a posttest-only control group design. VCO was made from grated fresh coconut and then mixed with NaCMC to obtain gel viscosity. The subjects of this study were 30 male periodontitis-induced Wistar rats by injecting Porphyromonas gingivalis into the gingival sulcus. Wistar rats were then divided into 3 groups. On the 7th and 14th days, the rats were sacrificed and the jaw was sampled to determine the amount of TNF-α and TGF-ß1 expression in the regenerative process of periodontal tissue. RESULT: The amount of TNF-α and TGF-ß1 increased significantly in the treatment group, but not as much as the increase in the positive control and negative control groups. CONCLUSION: VCO gel can affect the expression of TNF-α and TGF-ß1 in the regeneration process of periodontal tissue in periodontitis-induced rats.

Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress.

Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.

Effect of the Application of Chlorella Vulgaris Ointment to the Number of Fibroblast Cells as an Indicator of Wound Healing in the Soft Tissue of Pig Ears

Abstract Objective: To analyze the clinical and histological condition of Chlorella vulgaris ointment extract smearing on wound healing. Material and Methods: The sample consisted of 9 pigs by making 4 incisions on the pig's right ear measuring 2cm x 1cm and applying Chlorella vulgaris ointment in 3 concentrations namely 5%, 10%, 15% and without ointment application as the control group. Furthermore, the observation of the clinical condition of wounds divided into 4 time periods (day 1, 3, 7 and 14). After completing clinical observations based on time period, the skin of the pig's ear was taken by cutting in the area that had been made injured. Skin tissue extraction carried out under inhalation and local anesthesia. The tissue pieces are then processed in the anatomical pathology laboratory to become 36 slide preparations. The clinical trial assessment was done using parameters of wound moisture, color of wound and scab wound. Whereas for histological examination was done by looking at the number of fibroblast cells in the CX31 light microscope with 40x magnification. ANOVA and Kruskal Wallis tests were used. Results: In the clinical observation conditions there were significant differences between the treatment group and the control group as well as the number of fibroblast cells there were significant differences between the 3 concentrations of Chlorella vulgaris extract ointment and the per time period control group. Conclusion: Chlorella vulgaris extract ointment containing 15% extract gives the best results in accelerating the wound healing process in the pig's ear seen from wound healing and increased number of fibroblast cells.

Influence of Acrylic Resin Denture Base Soaking Length in Siwak Extract Solution (Salvadora persica) on the Growth of Candida albicans

Objective: To know the influence of immersion length of denture base of acrylic resin in Siwak solution (Salvadora persica) on Candida albicans growth. Material and Methods: This type of research is laboratory experimental. The Siwak plant (Salvadora persica) was extracted and 1% solution was formed. The media used were Sabouraud Dextrose Broth (SDB) and Sabouraud Dextrose Agar (SDA). Candida albicans was cultured as 1 dose in 100 ml of SDB medium, and then incubated at shaker rotation for 1x24 hours. The concentration chosen to test the effectiveness of siwak extract solution was 1%, 10%, 15% and 25%. Data were presented as mean ± SD. Results: Zone of 6 hours Siwak extract immersion inhibitor by 43.47 ± 0.35, 8 hours to know the influence of immersion length of denture base of acrylic resin in Siwak solution (Salvadora persica) on candida albicans growth 44.42 ± 0.02, 10 hours of 52.79 ± 0.03. Conclusion: There is a difference of immersion length of denture base of acrylic resin on Candida albicans growth in Siwak extract solution (Salvadora persica).

Efficacy of Mouthwash from Aloe vera Juice after Scaling Treatment on Patient with Gingivitis: A Clinical Study

Objective: To determine the effectiveness effectivity of mouthwash from Aloe vera juice after scaling treatment on patient with gingivitis. Material and Methods: This was an experimental research using pretest and posttest design with control group. The number of samples of 30 people selected using sampling method quota sampling. Samples were divided into two groups: test (n = 15 skeletons with Aloe vera juice) and control (n = 15 just scaling). Gingival inflammation is measured using a gingival index according to Loe and Sillness on the first day before scaling treatment and 7th day after scaling. Data analysis was conducted using SPSS version 20. Independent-samples t-test and paired-samples t-test were used for data analysis. The statistical test performed has a significance level of 0.05 (p = 0.05) and confidence level of 95% (α = 0,05). Results: There was a significant decrease in the mean score of the gingival index in the control group (1.1 to 0.5) and the test group (1.2 to 0.4) significantly (p<0.05). Conclusion: The use of mouthwash from Aloe vera juice can decrease gingival inflammation, which can be seen from the gingival index score on all test subjects. The decrease in gingival index in the test group using the Aloe vera juice was greater than that of the control group, which was not given the mouthwash.

Energy Dispersive Spectroscopy (EDS) Analysis of Calcium and Phosphor Minerals Elements on Bone After Insertion Immediate Implant on Socket Filled with Extract Aloe vera

Objective: To examine the effect of aloe vera that containing bioactive materials on the levels of calcium (Ca) and phosphorus (P) minerals and their ratios around the immediate implanted in alveolar bone. Material and Methods: Research method by conducting experimental test on experimental animals: 9 male mongrel dogs are divided into 3 groups each 3 tails. In each animal was pulled the second premolar teeth on right side and left side, and immediately inserted titanium implant (3mm x 10mm diameter) after the socket filled with 10% aloevera extract on the right side and control on the left side. Analysis of calcium and phosphorus minerals content formed by examination of Energy Dispersive Spectroscopy (EDS) on Scanning Electron Microscope on implant and around bone tissue was done on days 14, 28 and 56. The result of statistical analysis using repeated ANOVA with independent t test. The level of significance was set at 5%. Results: There was a significant difference on calcium level between control and treatment groups on days 14, 28 and 56 (p<0.05). There was no significant difference on phosphorus level between control and treatment groups (p>0.05). The ratio of Ca / P in both control and treatment groups was also significantly different in every observation day (p<0.05). Conclusion: The addition of aloe vera extract that containing bioactive materials has an effect on increasing levels of mineral elements calcium and calciumphosphorus ratio after immediate implant insertion.

Akt Signal Transduction Pathways and Nuclear Factor-kappa B (NF-κB) Transcription as a Molecular Target of Oral Tongue Squamous Cell Carcinoma (SP-C1) Using Papua's Anthill Plant ( Myrmecodia pendans ).

BACKGROUND AND OBJECTIVE: Squamous cell carcinoma is a malignant tumor derived from epithelial tissue with cell structure group, capable to infiltrate through the bloodstream and lymphatic tissue, spreading throughout the body. This study aim to complete theoretical foundation of flavonoid compound from anthill plant (Myrmecodia pendans) which contribute in growing cell line oral tongue squamous cell carcinoma through proliferation inhibition, inhibition mechanism transduction Akt signal and NF-κB in tongue cancer cell Supri's-clone (SP-C1). Application benefit to explore potential fractionation anthill plant use herbal ingredients for chemo protective therapy. MATERIALS AND METHODS: This whole study conducted with experiment laboratorium method utilized tongue cancer human cell SP-C1. This study consist 2 steps, first to determinate, extraction and fractionation anthill plant and carry out tonicity test to get flavonoid fraction from anthill plant which has anticancer potential against tongue cancer cell SP-C1. The second stage held with invasion inhibition test, proliferation and inhibition test against protein Akt expression and NF-κB in tongue cancer cell SP-C1. The barriers to proliferation through the test of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, barriers to invasion through Boyden chamber assay and the membrane polycarbonate, ELISA analysis and Western blotting analysis on the obstacle Akt signal transduction pathways and transcription factor of nuclear factor-kappa B (NF-κB). Data analysis conducted with 2 way ANOVA followed with LSD post hoc test with significance is set on 95%. Pearson correlation conduct to find strong relationship intervariable. RESULTS: This study showed that the average cell growth inhibition SP-C1 based on the time and concentration using the MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The resistance of cancer cell in vitro SP-C1. On ELISA testing and Western blotting analysis, inhibiton of protein expression of Akt signal transduction and transcription factor of nuclear factor-kappa B (NF-κB) showed increased protein expression was significantly obstacles and prove that the ethyl acetate fraction flavonoid inhibits translocation and activation of transcription pathway NF-κB and growth factors that induces the phosphorylation of Akt signal transduction pathway. CONCLUSION: Ethyl acetate fraction flavonoid anthill has antitumor activity in multiple molecular targets transduction pathway including Akt and nuclear factor-kappa B (NF-κB) squamous cell carcinoma of the tongue.