The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action. METHODS: A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed. RESULTS: Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics. CONCLUSION: Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.

The Value of Microbiome-targeted Therapy on Lipid Indices of Patients with Type 2 Diabetes Mellitus: An Umbrella Meta-analysis of Randomized Controlled Trials.

;Background: Type 2 diabetes mellitus (T2DM) is considered a global health challenge with increasing prevalence in recent years. One of the key elements in managing T2DM patients is controlling their lipid profile. Recent studies suggest microbiome-targeted therapy (MTT) as a treatment strategy for enhancing lipid profiles in these patients. OBJECTIVE: The current study aimed to investigate the impact of MTT on lipid indices of T2DM patients by performing an umbrella approach. METHODS: Three international databases including PubMed, Scopus, and Web of Sciences were searched from inception up to April 2023 to find meta-analyses evaluating the impact of MTT (prebiotics, probiotics, and synbiotics) on the lipid profile of T2DM patients. Two independent researchers extracted data from the relevant meta-analyses. To find the source of heterogeneity various subgroup analyses were performed. Comprehensive Meta-Analyses (CMA) software version 3 was utilized for the final analysis. RESULTS: Based on the results of the current study MTT had a significant effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) (ES: - 0.092; 95%CI: -0.111, -0.074; P< 0.001, ES: -0.109; 95%CI: -0.137, -0.081; P< 0.001, ES: -0.036; 95%CI: -0.068, -0.005; P= 0.024, ES: 0.109; 95%CI: 0.056, 0.162; P<0.000, respectively). In subgroup analysis, probiotics showed the most substantial effect on all lipid biomarkers. CONCLUSION: This research has provided promising insights into the potential impact of MTT on lipid levels in patients diagnosed with T2DM. Notably, MTT had the greatest impact on HDL levels, followed by TG, TC, and LDL. As a result of our study, MTT is recommended as an adjunctive therapeutic option for T2DM treatment due to its capability to regulate lipid profiles.

Effects of Vaccinium berries (blueberries, cranberries and bilberries) on oxidative stress, inflammation, exercise performance, and recovery - a systematic review.

Exercise-induced muscle damage is common in athletes and recreational exercisers and can lead to muscle soreness, weakness, and impaired muscle function. The precise mechanisms are unclear but oxidative stress and inflammation are thought to play a role. (Poly)phenols are substances abundant in Vaccinium berries that have been suggested to possess antioxidant and anti-inflammatory effects that could help improve exercise performance and/or recovery from exercise. The objective of this systematic review was to evaluate the benefits of Vaccinium berry supplementation on exercise performance and recovery, as well as on exercise-induced oxidative and inflammatory biomarkers in healthy individuals. A comprehensive search was conducted in PubMed, ProQuest Medline, Web of Science, Cochrane Library, and Scopus. Studies were included if the participants were healthy individuals who were supplemented with any Vaccinium berry or Vaccinium berry-based products in comparison to a control group. Of the 13 articles included in this review, no significant differences in the exercise performance were found and only one study reported benefits for markers of recovery. Interleukins and c-reactive protein were the most frequently reported biomarkers, but there was limited evidence that Vaccinium berry supplementation impacted them post-exercise. Most studies were of high quality and showed a low risk of bias. Vaccinium berry supplementation is not effective in modulating markers of exercise-induced inflammation and oxidative distress in healthy individuals; nevertheless, more studies are required to evaluate their effects on exercise performance and recovery in this population.

The effectiveness of walking exercise on the bowel preparation before colonoscopy: a single blind randomized clinical trial study.

BACKGROUND AND AIM: Bowel preparation is a crucial factor affecting the diagnostic accuracy of colonoscopy, and few randomized control trials evaluated enhancement in bowel preparation. In this study, we aimed to evaluate the effectiveness of walking exercises on bowel preparation before a colonoscopy procedure. METHODS: The present study is a single-blind randomized controlled trial involving 262 patients scheduled for colonoscopy procedures. These patients were randomly assigned to two groups: an intervention group (n = 131) and a control group (n = 131). In the intervention group, participants followed a predetermined plan that included the consumption of specific liquids and foods, bisacodyl pills, polyethylene glycol powder, and a regimen of walking exercises in preparation for their colonoscopy. Conversely, individuals in the control group followed the same regimen but were not instructed to engage in walking exercises. On the day of the colonoscopy, both groups were assessed for their level of physical activity using a foot counter. Additionally, an experienced gastroenterologist evaluated and compared the bowel preparation between the two groups using the Boston Bowel Preparation Scale (BBPS). RESULTS: The number of footsteps recorded in the two groups exhibited a significant difference (P < 0.001). Although there was no statistically significant difference between the intervention and control groups in terms of mean BBPS scores (6.26 ± 1.9 vs. 6.29 ± 1.9, P = 0.416), individuals who took more than 6900 steps had significantly higher BBPS scores compared to those with fewer than 6900 footsteps (6.62 ± 1.8 vs. 5.92 ± 1.9, P = 0.003).In the univariate analysis, BBPS was found to be significantly associated with individuals under the age of 50 (OR: 2.45, 95% CI: 1.30-4.61, P = 0.006) and smoking status (OR: 0.41, 95% CI: 0.17-0.94, P = 0.043). In the multivariate analysis, the relationship between BBPS and age below 50 and smoking remained significant (OR: 2.50, 95% CI: 1.30-4.70, P = 0.005, and OR: 0.38, 95% CI: 0.16-0.93, P = 0.034, respectively). CONCLUSION: A higher number of footsteps taken especially more than 6900 can significantly enhance bowel preparation; however, walking exercise as an intervention before colonoscopy is not significantly associated with BBPS. Also, older people and smokers seem to have fewer benefits from walking exercises for bowel preparation. TRIAL REGISTRATION: ISRCTN32724024 (Registration date:22/08/2018).

Effect of Soy Protein Supplementation on Muscle Adaptations, Metabolic and Antioxidant Status, Hormonal Response, and Exercise Performance of Active Individuals and Athletes: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: Protein supplements are important to maintain optimum health and physical performance, particularly in athletes and active individuals to repair and rebuild their skeletal muscles and connective tissues. Soy protein (SP) has gained popularity in recent years as an alternative to animal proteins. OBJECTIVES: This systematic review evaluates the evidence from randomised controlled clinical trials of the effects of SP supplementation in active individuals and athletes in terms of muscle adaptations, metabolic and antioxidant status, hormonal response and exercise performance. It also explores the differences in SP supplementation effects in comparison to whey protein. METHODS: A systematic search was conducted in PubMed, Embase and Web of Science, as well as a manual search in Google Scholar and EBSCO, on 27 June 2023. Randomised controlled trials that evaluated the applications of SPs supplementation on sports and athletic-related outcomes that are linked with exercise performance, adaptations and biomarkers in athletes and physically active adolescents and young adults (14 to 39 years old) were included, otherwise, studies were excluded. The risk of bias was assessed according to Cochrane's revised risk of bias tool. RESULTS: A total of 19 eligible original research articles were included that investigated the effect of SP supplementation on muscle adaptations (n = 9), metabolic and antioxidant status (n = 6), hormonal response (n = 6) and exercise performance (n = 6). Some studies investigated more than one effect. SP was found to provide identical increases in lean mass compared to whey in some studies. SP consumption promoted the reduction of exercise-induced metabolic/blood circulating biomarkers such as triglycerides, uric acid and lactate. Better antioxidant capacity against oxidative stress has been seen with respect to whey protein in long-term studies. Some studies reported testosterone and cortisol fluctuations related to SP; however, more research is required. All studies on SP and endurance performance suggested the potential beneficial effects of SP supplementation (10-53.3 g) on exercise performance by improving high-intensity and high-speed running performance, enhancing maximal cardiac output, delaying fatigue and improving isometric muscle strength, improving endurance in recreational cyclists, increasing running velocity and decreasing accumulated lactate levels; however, studies determining the efficacy of soy protein on VO2max provided conflicted results. CONCLUSION: It is possible to recommend SP to athletes and active individuals in place of conventional protein supplements by assessing their dosage and effectiveness in relation to different types of training. SP may enhance lean mass compared with other protein sources, enhance the antioxidant status, and reduce oxidative stress. SP supplementation had an inconsistent effect on testosterone and cortisol levels. SP supplementation may be beneficial, especially after muscle damage, high-intensity/high-speed or repeated bouts of strenuous exercise.

Dynamic Rod Constructs as the Preventive Strategy against Adjacent Segment Disease in Degenerative Lumbar Spinal Disorders: A Retrospective Comparative Cohort Study.

Objectives: Adjacent segment degeneration (ASDe) and adjacent segment disease (ASDi) are potential long-term complications after lumbar fusion with rigid instrumentation. Dynamic fixation techniques (Topping-off) adjacent to the fused segments have been developed to curtail the risk of ASDe and ASDi. The current study sought to investigate whether the addition of dynamic rod constructs (DRC) in patients with preoperative degeneration in the adjacent disc was effective in reducing the risk of ASDi. Methods: A retrospective analysis was performed on clinical data of 207 patients with degenerative lumbar disorders (DLD) from January 2012 to January 2019, who underwent posterior transpedicular lumbar fusion (without Topping-off, NoT/O), and posterior dynamic instrumentation with DRC. Clinical and radiological outcomes were evaluated using Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), and lumbar radiographs one, three, and 12 months postoperatively and annually. ASDe was defined as disc height collapse > 20% and disc wedging > 5. Patients with confirmed ASDe and aggravation of ODI > 20 or VAS score > 5 at final follow-up were diagnosed as ASDi. The Kaplan-Meier hazard method was used to estimate the cumulative probability of ASDi within 63 months of surgery. Results: Over three years of follow-up, 65 patients in the NoT/O (59.6%) and 52 cases (53.1%) in the DRC groups met the diagnostic criteria for ASDe. Furthermore, 27 (24.8%) patients in the NoT/O group showed ASDi during the follow-up, compared to 14 (14.3%) cases in the DRC group (P=0.059). Revision surgery was performed on 19 individuals in the NoT/O and 8 cases in the DRC groups (P=0.048). The Cox regression model identified a significantly decreased risk of ASDi if DRC was used (Hazard ratio: 0.29; 95% CI: 0.13-0.6). Conclusion: Dynamic fixation adjacent to the fused segment is an effective strategy for preventing ASDi in carefully selected individuals with preoperative degenerative changes at the adjacent level.

How can chokeberry (Aronia) (poly)phenol-rich supplementation help athletes? A systematic review of human clinical trials.

Athletes are increasingly consuming (poly)phenol supplements to modify oxidative stress and/or exercise-induced inflammation, in the hope that this will enhance exercise performance. Chokeberries are rich in (poly)phenols and may therefore influence the health and performance of athletes. The objective of this systematic review was to comprehensively explore the effects of chokeberry supplementation on performance and exercise-induced biomarkers of oxidative stress, inflammation, and haematology in the athletic population. A search was conducted in PubMed, Web of Science, and SCOPUS. Studies were included if the participants were athletes, supplemented with chokeberry or chokeberry-based products, and evaluated sports-related outcomes. A total of ten articles were included in the study. The participants of all the studies were athletes and included rowers, football players, handball players, triathletes, and runners. A qualitative comprehensive summary of the applications of chokeberry supplementation targeting the athletic population has been evaluated. This included the effect of chokeberry supplementation on redox status, exercise-induced inflammation, haematology, iron metabolism, platelet aggregation, metabolic markers, body composition, and exercise performance. Chokeberry (poly)phenol-rich supplementation may be effective in enhancing the redox balance of athletes, yet more evidence is required to provide solid conclusions on its effect on inflammation, platelet function, iron metabolism and exercise performance.

Survival rate of thyroid cancer in the Asian countries: a systematic review and meta-analysis study.

PURPOSE: Overall, thyroid cancer is the most common endocrine malignancy. This cancer is fifth most common cancer among adult women and the second most common cancer in women over 50 years old and it occurs in women 3 times more than men. The present systematic review and meta-analysis were designed with the aim of determining the 5-year survival rate of thyroid cancer in Asian countries in 2022. METHODS: The current study is a systematic review and meta-analysis of thyroid cancer survival rates in Asian countries. Researchers in the study searched for articles published in six international databases: PubMed/Medline, EMBASE, Scopus, Google Scholar, ISI (Web of Knowledge), and ProQuest until July 03, 2022. A checklist (The Newcastle-Ottawa Quality Assessment Form) has been prepared in previous studies to evaluate the quality of articles. RESULTS: In general, 38 articles were entered for the meta-analysis. The 5-year survival rate was 95.3%, with a 95% confidence interval of 93.5% to 96.6%. The year of study is a cause of variability in results of 5-year (Reg Coef = 0.145, P < 0.001). According to the results, an increased survival rate across the study period was observed. Human Development Index was a cause of variability in results of 5-year survival rates (Reg Coef = 12.420, P < 0.001). The results of Table 2 showed that women have 4% more 5-year survival rate than men (Hazard ratio: 1.05 CI: 95% 1.04-1.06)). CONCLUSION: In general, the 5-year survival of thyroid cancer in Asian countries was higher than in European countries, but it is at a lower level than in the United States.

The bFGF Can Improve Angiogenesis in Oral Mucosa and Accelerate Wound Healing.

Background: The role of the basic fibroblast growth factor (bFGF) has well known in the angiogenesis and ulcer healing. In this study, we aimed to evaluate the effects of bFGF on tissue repair in a rat oral mucosal wound. Methods: Musosal wound induced on the lip mucosa of rats and bFGF was injected along the edge of the mucosal defect immediately after surgery. The tissues were collected on days 3, 7 and 14 after the wound induction. The micro vessel density (MVD) and CD34 expression were done by histochemical studies. Results: The bFGF significantly accelerated granulation tissue formation and MVD was increased three days after ulcer induction but decreased 14 days after surgery. The MVD was significantly higher in the bFGF-treated group. The wound area was decreased in all groups time-dependently and a statistically significant difference (p value?) was observed between the bFGF-treated group and untreated group. The wound area was smaller in the bFGF-treated group compared to the untreated group. Conclusions: Our data demonstrated that bFGF can accelerated and facilitated wound healing.

Intraparenchymal Schwannoma of Temporal Lobe: A Case Report and Review of the Literature.

Intracranial schwannomas (ISs) account for approximately 8% of intracranial tumors, while IS, a rare entity, is responsible for roughly 1% of IS. A 33-year-old man with a 3-month headache and sudden onset seizure was referred to our clinic. Preoperative magnetic resonance imaging revealed a contrast-enhancing mass accompanied by cystic components in the right temporal lobe. Ganglioglioma, metastasis, or glioblastoma multiforme was suspected, and surgery was advised. During surgery, gross total resection of a noninvasive tumor was conducted. Postoperative recovery was uneventful. Based on histopathological examination and confirmatory immunohistochemistry, the intraparenchymal temporal tumor was diagnosed as schwannoma. ISs are extremely scarce brain tumors mainly located on the surface of the brain or adjacent brain ventricles. The definite preoperative diagnosis of schwannoma cannot be readily established due to radiologically indistinguishable features from metastasis and gliomas; however, histopathology and immunohistochemistry are of great assistance. Complete surgical removal is the most preferred treatment alternative with a long-term favorable prognosis without adjuvant and neoadjuvant chemotherapy requirements.

The organoid as reliable cancer modeling in personalized medicine, does applicable in precision medicine of head and neck squamous cell carcinoma?

Head and neck squamous cell carcinomas (HNSCCs) are introduced as the sixth most common cancer in the world. Detection of predictive biomarkers improve early diagnosis and prognosis. Recent cancer researches provide a new avenue for organoids, known as "mini-organs" in a dish, such as patient-derived organoids (PDOs), for cancer modeling. HNSCC burden, heterogeneity, mutations, and organoid give opportunities for the evaluation of drug sensitivity/resistance response according to the unique genetic profile signature. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) nucleases, as an efficient genome engineering technology, can be used for genetic manipulation in three-dimensional (3D) organoids for cancer modeling by targeting oncogenes/tumor suppressor genes. Moreover, single-cell analysis of circulating tumor cells (CTCs) improved understanding of molecular angiogenesis, distance metastasis, and drug screening without the need for tissue biopsy. Organoids allow us to investigate the biopathogenesis of cancer, tumor cell behavior, and drug screening in a living biobank according to the specific genetic profile of patients.

Association between Tissue Expression of Toll-Like Receptor and Some Clinicopathological Indices in Oral Squamous Cell Carcinoma.

Background: The oral squamous cell carcinoma (OSCC) composes about 90% of all head and neck cancers. The toll-like receptor (TLR)+ immune cells have potential of invasion and malignancy transformation. The aim of this study was assessment of possible associations between clinicopathological indices and TLR2 and TLR9 gene expression in OSCC. Methods: Forty-two OSCC samples with related healthy margins including 25 early and 17 advanced stages were gathered. The samples were classified histologically from grade I to II. The expression of TLR2 and TLR2 was evaluated by Real-time PCR. The patient's disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS V.23 software. Results: The expression of TLR2 and TLR9 genes in tumor tissues (especially in grade I and II) were higher than healthy surgical margin tissue (p< 0.001). TLR9 expression in grade II was statistically significant than grade I in tumor tissue (p< 0.001). TLR9 expression in advanced stage was statistically significant in compare to early stage (p= 0.012). In advanced stage both overall survival (p= 0.029) and disease-free survival (p= 0.012) were statistically lower than early stage. The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007). Conclusion: Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.

Launching Awake Craniotomy Technique in a Resource-Limited Center: New Insights into the Patient Experience, Costs, and Long-Term Outcomes and a Narrative Review of the Literature.

BACKGROUND: Awake craniotomy (AC) with brain mapping is a standard surgical technique for the excision of lesions located in eloquent areas. We aimed to assess the clinical challenges, patient experience, costs, and long-term outcomes of AC in a resource-limited setting. METHODS: In this cross-sectional study, electronic documents of 12 patients who underwent AC with functional brain mapping were prospectively collected from August 2017 to October 2020. Patient characteristics, surgical specifications, hospitalization period, intraoperative and postoperative events, functional outcome, patients' satisfaction, costs, and survivals were collected and analyzed. RESULTS: Twelve patients with a median age of 42.5 (interquartile range, 13.5) were enrolled, of whom 8 were male (66.7%), and 9 (75%) were harboring grade 2 glioma. Of the patients, 8.34%, 33.34%, and 58.33% had partial, subtotal, and gross total excision of the tumors, respectively. The intraoperative seizure was the only complication and occurred in 2 cases (16.67%). At 1 year follow-up, none of the patients experienced any neurologic deficit. Eleven patients (91.6%) had a satisfactory opinion about reappearing in the AC. At 38 months follow-up, mortality was 8% for AC group and 25% among the historically matched controls who had surgery under general anesthesia (P = 0.27). Most costs belonged to the neurosurgery team (43%), and the overall expenses were reduced by 13% compared with a putatively well-equipped setting in our country. CONCLUSIONS: In carefully selected individuals, AC with brain mapping for excision of gliomas could be a safe, effective, and affordable strategy in a resource-limited setting and can be successfully performed with satisfactory outcomes.

Memory and executive functioning outcomes of selective amygdalohippocampectomy in patients with hippocampal sclerosis: A preliminary study in a developing country.

Background: Selective amygdalohippocampectomy (SA) is an effective treatment for drug-resistant cases of epilepsy due to hippocampal sclerosis (HS). However, its neurocognitive outcomes are inconsistent across the previous studies, pointing to potential location-specific confounders. Here, we investigated the neurocognitive outcomes of SA in an Iranian center recently adopting this approach. Methods: Thirty adults (53.3% of females, age 31.4 ± 6.2 years) with drug-resistant epilepsy due to HS were included in the study. Patients were stratified into surgical (n = 15) and medical (n = 15) treatment groups based on their preferences. Neurocognitive function was assessed before and 6 months after intervention using Wisconsin Card Sorting Test (WCST), Wechsler Adult Intelligence Scale-Revised, and Wechsler Memory Scale- Third Edition (WMS-III). Postintervention performance changes were compared between the two groups, and predictors of worse postoperative outcomes were investigated. Results: Longitudinal changes of performance in WMS-III and WCST were significantly different between the surgically and medically treated patients. Postoperative WMS-III performance showed an average 25% decline (mean ∆T2-T1 = -25.1%, T = -6.6, P < 0.001), and WCST performance improved by an average of 49% (mean ∆T2-T1 = +49.1%, T = 4.6, P < 0.001). The decline in memory performance was more severe in the left-sided surgery and in patients with higher baseline education (mean ∆T2-T1 = -31.1%, T = -8.9, P < 0.001). Conclusion: In our center, executive functioning improved or remained stable after SA, but memory functions declined moderately. The left-sided SA and higher education were associated with more severe decline in memory functions, highlighting the need for special considerations for these groups.

Tumor tissue Helicobacter pylori and human papillomavirus infection in head and neck squamous cell carcinoma patients and association with clinicopathological indices: A cross-sectional medical survey.

Background: The associations between Helicobacter pylori and human papillomavirus (HPV) with head and neck squamous cell carcinomas (HNSCCs) are approved before. However, the association between demographic, clinicopathological, and histologic characteristics of HNSCC patients and molecular detection of HPV and H. pylori has not been enough investigated. Materials and Methods: In this cross-sectional study, 62 patients with HNSCC from January 2016 to February 2020 were entered the study. For H. pylori detection 16S ribosomal RNA and glmM genes and HPV detection, MY09 and MY11 genes were used. P < 0.05 is considered as significant level. Results: There were 34 patients with advanced-stage cancer (54.8%). Grade I patients (61.3%) had the highest frequency. There were 20 (32.25%) and 7 (11.29%) patients with positive H. pylori infection among tumor tissue and healthy tissue margins, respectively. Positive HPV infections were in 8 (12.90%) and 3 (4.83%) patients, respectively, in tumor tissue and healthy tissue margins (P = 0.01). There was a significant difference between histological grade and infection to HPV among HNSCC patients (P = 0.01), and most of the positive HPV cases had well-, moderate-, and poorly-differentiated tumors, respectively. Our study showed a significant increase in HPV infection in the advanced-stage group compared to the early-stage group (P = 0.05). Conclusion: Our study findings concluded a significant relationship between HPV infection in HNSCC patients with age, stage, and grade. In summary, our findings based on polymerase chain reaction analysis concluded remarkably a potential role of HPV infection and to some extent H. pylori infection into the contribution of HNSCC malignancies.

Neglected alkaptonuric patient presented with low back pain and radiculopathy: A case report.

BACKGROUND: Alkaptonuria (AKU) is a rare hereditary disorder in which excess homogentisic acid (HGA) deposits in connective tissues (ochronosis). Here, we report the unusual presentation of a lumbar disc herniation occurring in a patient with AKU warranting surgical intervention. CASE DESCRIPTION: A 28-year-old male presented with 1 year of low back pain. The lumbar magnetic resonance imaging showed an extruded disc at the L4-L5 level accompanied extensive disc space narrowing and osteophyte formation. At surgery, the interspinous ligaments, facet joints, and disc herniation were black. In addition, the postoperative re-examination revealed a black discoloration of the nasal and ear cartilage. Finally, the diagnosis of AKU was confirmed when the urine specimen was positive for HGA. CONCLUSION: Rarely, younger patients with AKU who develop excess black deposits of HGA in connective tissues (i.e., ochronosis) may present with lumbar disc herniations and spondylosis.

Evaluation of correlation between transcription factors and IL-17 in oral and cutaneous lichen planus lesions and Leukocytes.

BACKGROUND: Lichen planus (LP) is a chronic autoimmune disease with different clinical subtypes including cutaneous LP (CLP) and oral LP (OLP). We aimed to compare mRNA expression of RORγt and IL-17 in paraffin-embedded blocks of OLP and CLP lesions with normal oral mucosa (NOM), and also its correlation with hematologic parameters. MATERIALS & METHODS: This study included 89 paraffin-embedded blocks contain OLP (44 cases), CLP (45 cases) and NOM from the archive of Mashhad University of Medical Sciences, Mashhad, Iran. The expression of RORγt and IL-17 was evaluated by Real-time RT-PCR method. The result was compared to Leukocyte counts and the other hematological parameters of studied patients. RESULTS: The results of our study showed IL-17 and RORγt expression in OLP lesions were significantly higher than CLP and NOM groups (P = 0.001). Although we found high expression of RORγt and IL-17 in erosive OLP in compared to classic OLP lesion, but this increment was not significant for IL-17 (P = 0.26) and RORγt (P = 0.14). Further, Leukocyte and monocyte counts were substantially high in OLP group in compared to the CLP and NOM groups (P < 0.05). CONCLUSIONS: We concluded that increased expression of RORγt and IL-17 in LP lesions could play role in the pathogenesis of LP. As well, higher expression of RORγt and IL-17 in oral LP more than cutaneous LP might be associated with difference in clinical behavior of the two types of disease and role of these factors in premalignant behavior of OLP lesions.

Cytokeratins (CK7 and CK20) Genes Expression Association with Clinicopathological Indices in Oral Squamous Cell Carcinoma and Dysplastic Oral Epithelium.

BACKGROUND: High prevalence of oral squamous cell carcinoma (OSCC) demands the additional novel biological markers. Due to the established roles of cytokeratin in the prognosis of metastasis evaluation the relation of expression of both CK7 and CK20 in OSCC compared to the dysplastic oral epithelium biopsies with clinicopathological factors were investigated. METHODS: We examined the coordinate mRNA expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 110 biopsies of oral squamous epithelium samples including 72 tumoral and 38 dysplastic biopsies. We also collected demographic and pathological data including tumor stage and grade from our patients. RESULTS: There was a significant difference in CK7 and CK20 gene expression between OSCC and dysplastic samples (p< 0.001). Further, their mean expression in OSCC samples was significantly higher compared to dysplastic samples. Relative mRNA levels of CK7 and CK20 showed that their mean expression in OSCC grade I was significantly lower than other grades (p< 0.01). The relationship between CK7 and CK20 mRNA expression and age or gender was not significant (p> 0.05). Samples in the advanced stage of disease had significantly higher CK7 and CK20 expression compared to early-stage samples of OSCC specimens (p= 0.001). CONCLUSION: We found an increase in CK7 and CK20 mRNA levels in grade III OSCC samples compared to other grades. This finding suggests a potential role for CK7 and CK20 in oral mucosal carcinogenesis and OSCC prognosis.

LAMP3 (CD208) Expression in Squamous Cell Carcinoma and Epithelial Dysplasia of the Oral Cavity and Clinicopathological Characteristics of Unfavorable Prognosis.

BACKGROUND: This study aimed to evaluate LAMP3 (CD208) gene expression in oral squamous cell carcinoma (OSCC) and dysplastic oral epithelium by quantitative real-time polymerase chain reaction (qPCR) and compare LAMP3 expression in different disease grades and stages. METHODS: In this study, 60 OSCC and dysplastic oral epithelium samples were obtained from the Mashhad University of Medical Sciences together with their demographic and clinicopathological documents. LAMP3 expression was measured by qPCR. RESULTS: LAMP3 expression was significantly greater in OSCC than in dysplasia samples (P=0.001), in grade III OSCC than in grades I and II, and also greater in advanced than in early OSCC disease stage (P=0.001). CONCLUSION: The significantly greater LAMP3 expression in OSCC than in dysplastic epithelium indicates a role for LAMP3 in carcinogenesis in oral mucosa. Our results suggest LAMP3 may be useful as an anticancer target and/or to predict disease pathogenesis in OSCC patient's cells.

New diagnostic molecular markers and biomarkers in odontogenic tumors.

Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of odontogenic tumors is not exactly determined and pathologists deal with challenges in diagnosis of odontogenic tumors because they are rare and obtained experiences are difficult to evaluate. In this study, we describe immunohistochemical and molecular markers in diagnosis of odontogenic tumors besides advanced diagnostic technique. Immunohistochemical features of odontogenic tumors beside the clinical features and radiological finding can help us to determine the correct diagnosis. Although these markers are neither specific nor sensitive enough, but analysis of gene expression provides definitive confirmation of diagnosis. In addition, "-omics" technology detected specific molecular alternation associated with etiology such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. The post transcriptional events such as DNA methylation and chromatin remodeling by histone modification affect the changes in epigenome. Furthermore, non-coding RNAs like micro-RNAs, long noncoding RNA (lncRNA) and small non-coding RNA (snoRNA) play regulatory role and impact odontogenesis. Molecular marker propose their potential role in etiopathogenesis of odontogenic tumors and suitable candidate in diagnostic, prognostic and therapeutic approaches in addition to patient management. For future evaluations, organoid represents in vitro tumor model-study for tumor behavior, metastasis and invasion, drug screening, immunotherapy, clinical trial, hallmarks association with prognosis and evolution of personalized anti-cancer therapy. Moreover, organoid biobank help us to check genetic profile. We think more investigation and studies are needed to gain these knowledges that can shift therapeutic approaches to target therapy.