Oral hyperpigmentation as an adverse effect of highly active antiretroviral therapy in HIV patients: a systematic review and pooled prevalence

Human Immunodeficiency Virus (HIV) infects patients via CD4+ cells which are later be destroyed subsequently causing the deteriotation of immune system. HIV generally manifests in the oral cavity as the first indicating sign and a marker of disease progression. HAART medications are used to reduce the incidence of oral manifestations, however it can also generate adverse effects in the oral cavity including oral hyperpigmentation. This review aimed to estimate the prevalence of oral hyperpigmentation which affect individual quality of life as a side effect of HAART.This systematic review applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020. Literature search was performed in ScienceDirect, PubMed, and Scopus by combining terms such as highly active antiretroviral therapy, oral manifestation, epidemiology or prevalence published between January 1998 to March 2022.Of 108 articles, eleven articles were included for systematic review and meta-analysis. The pooled prevalence of oral hyperpigmentation in HAART patients was 25% (95% CI: 11%, 38%; I2: 99%). Subgroup analysis based on geographical location showed varied result may be due to the type and duration of HAART used in study population. The most widely used type of ARV was from the NRTI group (n=7) and the study with the shortest duration showed the lowest oral hyperpigmentation prevalence (n=7).There is an increased prevalence of oral hyperpigmentation by the use of HAART. Future study should investigate the correlation between HAART duration and the degree of oral hyperpigmentation

Oral cancer : a multicenter study

To determine the prevalence and clinicopathologic features of the oral cancer patients. Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients

MMP-13 Promotes Tumor Angiogenesis

Background: Angiogenesis is an important step in the metastatic cascade of tumors. Results: MMP-13 itself as well as VEGF-A secretion from fibroblasts promotes angiogenesis. Indeed, MMP-13 is well correlated with blood vessel density in human cancer tissues. Conclusion: MMP-13 can be a marker for prediction of malignant behaviors and a therapeutic target in cancer. Significance: This work provides new insights regarding the role of MMP-13 in tumor angiogenesis

Perceptions of Online Learning Implementation in Dental Education during the COVID-19 Pandemic: A Cross-Sectional Study of Dental School Faculty Members in Southeast Asia

Objective: To assess the perceptions of faculty members from dental schools in Southeast Asian countries regarding the implementation of online learning during the COVID-19 pandemic. Methods: A previously implemented questionnaire comprising 43 questions was utilized in this study. Lecturers from four universities in Southeast Asia were invited to participate in the study. Statistical analysis: The data were analyzed using SPSS version 25.0 through several types of comparative and correlation analyses. Results: There were 183 lecturers who participated in the study. The overall responses suggest that the perceived effectiveness of online learning in dentistry was centered on a neutral value. The participants faced challenges when implementing online learning during the COVID-19 pandemic, with the lack of interaction being the most challenging factor. They agreed that online learning had many advantages, specifically in time flexibility and communication. The participants had stronger perceptions relating the advantages and opportunities of online teaching, and recognized that the effectiveness of offline teaching alone was limited. Conclusion: The perceptions of Southeast Asian dental school faculty members were inclined toward a positive outlook on blended learning for implementation in dentistry, as a means of providing opportunities to use online learning beyond COVID-19 in the future

Molecular mechanism of inhibitory effects of bovine lactoferrin on the growth of oral squamous cell carcinoma

<div><p>Background</p><p>Lactoferrin (LF), a member of the transferrin family, recently has been demonstrated to have anticancer effects on various cancers including oral squamous cell carcinoma (OSCC). However, little is known about the underlying mechanisms of its effects on OSCC. Therefore, we aimed to investigate the mechanism of the suppressive effects of bovine LF (bLF) on the growth of OSCC cells.</p><p>Methods</p><p>In the current study, HSC2, HSC3, HSC4 and normal human oral keratinocytes (RT7) cell lines were tested with bLF 1, 10, and 100 μg/ml. The effects and detail mechanisms of bLF on proliferation and apoptosis of cells were investigated using flow cytometry and western blotting.</p><p>Results</p><p>We found that bLF (1, 10, and 100 μg/ml) induced activation of p53, a tumor suppressor gene, is associated with the induction of cell cycle arrest in G1/S phase and apoptosis in OSCC. Moreover, bLF downregulated the phosphorylation of Akt and activated suppressor of cytokine signaling 3 (SOCS3), thereby attenuating multiple signaling pathways including mTOR/S6K and JAK/STAT3. Interestingly, we revealed that bLF exerted its effect selectively against HSC3 but not on RT7 via different effects on the phosphorylation status of NF-κB and Akt.</p><p>Conclusion</p><p>This is the first report showing that bLF selectively suppresses proliferation through mTOR/S6K and JAK/STAT3 pathways and induction of apoptosis in OSCC. This study provides important new findings, which might be useful in the prevention and treatment of OSCC.</p></div

Schema of inhibitory effects of bLF on growth of OSCC cells and its underlying molecular mechanisms.

<p>In OSCCs, bLF internalizes into cells through LRP1 and suppressed NF-kB p65/Akt pathways. The attenuation of p65/Akt by bLF may inhibit G1/S cell cycle through the inhibition of downstream signaling pathways including mTOR/S6K and STAT3 and induce apoptosis in OSCC. Moreover, SOCS3, which is a negative regulator of STAT3, is upregulated. The overexpression of of SOCS3 in OSCC by bLF may downregulate JAK2/STAT3 pathway leading to the induction of G1/S cell cycle arrest.</p

Effect of bovine lactoferrin on the proliferation of OSCC and normal mucosal cells.

<p>OSCC and RT7 cells were treated with different concentrations of bLF (1 μg/ml, 10 μg/ml, and 100 μg/ml) and cell number was counted on days 1, 2, 4 and 6. bLF significantly prohibited the cell proliferation of OSCC cell lines in a dose-dependent manner; (<b>A</b>) HSC2, (<b>B</b>) HSC3, and (<b>C</b>) HSC4. bLF did not affect the cell growth of RT7 cells (<b>D</b>). Data represented as mean ± S.D; * p < 0.05 and ** p < 0.01 <i>vs</i> control (0 μg/ml of bLF).</p

Bovine lactoferrin suppressed the phosphorylation of growth and survival related kinase NF-kB p65 and Akt in HSC3 cells.

<p>HSC3 cells were treated with different concentrations of bLF. (<b>A</b>) After 48 h, bLF inhibited the activation of growth and survival related kinase p65 and Akt in HSC3 cells. (<b>B</b>) Number of HSC3 cells treated with and without CAPE 10μg/ml and bLF were counted. (<b>C</b>) G1/S cell cycle arrest related proteins were observed using western blot. (<b>D</b>) Proliferation assay were conducted using HSC3 cells under treatment of LY294002 (10 μM) and bLF (100 μg/ml). Cells were counted on day 1, 2, 4, and 6. (<b>E</b>) G1/S cell cycle related molecules were examined using western blot after 48 h stimulations of LY294002 and bLF. β-actin was used as loading control. Image is representative of 3 independent experiments (n = 3).</p

Bovine lactoferrin induced apoptosis in OSCC cells.

<p>(<b>A</b>) To check the effect of bLF on cell apoptosis, HSC3 cells were incubated with bLF (1 μg/ml, 10 μg/ml, and 100 μg/ml) for 48 h. Percentage of apoptotic cells were then analyzed by flow cytometry using PE Annexin V and 7-AAD. Cell populations were analyzed in four quadrants, Q1: necrotic cells, Q2: late apoptotic cells, Q3: viable cells, and Q4: early apoptotic cells. Total apoptotic cells were measured as the sum of early and late apoptotic cells. A dose-dependent increase in apoptotic cell number was observed after bLF treatment. Data were shown as the mean ± S.D (n = 3); * p < 0.05, ** p < 0.01 vs control. (<b>B</b>) HSC3 cells were treated with or without bLF (1, 10, and 100 μg/ml) for 48 h. Expressions of apoptosis-related genes were analyzed by western blotting. bLF treatment inhibited the phosphorylation of BAD and Bcl2 in HSC3 cells whereas expression of cleaved caspases 9, 3, 6, and 7 was upregulated. β-actin was used as a loading control. Data are representative of 3 independent experiments (n = 3).</p

Bovine lactoferrin inhibited expression of mTOR and S6K pathway thereby suppressed growth in HSC3 cells.

<p>HSC3 cells were treated with (1 μg/ml, 10 μg/ml, and 100 μg/ml) or without bLF. (<b>A</b>) Protein levels of p-mTOR and p-S6K were investigated by western blot after 48 h of stimulations. Expression of phosphorylated mTOR and S6K was decreased after bLF treatment. (<b>B</b>) To check the combinatorial effect of bLF and the inhibitor of mTOR, rapamycin, HSC3 cells were treated with 10 nM of rapamycin along with 100 μg/ml of bLF. No additive change was observed on p-mTOR and p-S6K expressions as shown by western blot. (<b>C</b>) Number of HSC3 cells was counted on day 1, 2, 4, and 6 with and without rapamycin and bLF. No additional effects on growth of cells in rapamycin and its combination. (<b>D</b>) G1/S cell cycle related molecules were investigated using western blot after 48 h of stimulations. Either rapamycin (10 nM) or its combination with bLF accumulated p21 expression but suppressed cyclin D1. (<b>E</b>) The growth of HSC3 cells was investigated under treatments of PF-4708671 (10 μM) and bLF 100 μg/ml. PF-4708671 remarkably attenuated number of HSC3 cells. There were no differences in number of cells between PF-4708671 and PF-4708671 with bLF. (<b>F</b>) Protein expression of p21 and cyclin D1 were examined using PF-4708671. PF-4708671 induced G1/S cell cycle arrest in HSC3 cells whereas no additive changes in the expressions p21 and cyclin D1 between PF-4708671 and its combination with bLF. β-actin was used as a loading control. The blots represent 3 independent experiments.</p