Role of Oral Microbiota in Carcinogenesis: A Short Review

A strong and healthy microbiome is responsible for homeostasis between the host and microbiota which is necessary to achieve the normal functioning of the body. Dysbiosis provokes prevalence of pathogenic microbes, leading to alterations in gene expression profiles and metabolic processes. This in turn results in anomalous immune responses of the host. Dysbiosis may be associated with a wide variety of diseases like irritable bowel syndrome, coeliac disease, allergic conditions, bronchitis, asthma, heart diseases and oncogenesis. Presently, the links between oral microbial consortia and their functions, not only in the preservation of homeostasis but also pathogenesis of several malignancies have gained much awareness from the scientific community. The primary intent of this review is to highlight the dynamic role of oral microbiome in oncogenesis and its progression through various mechanisms. A literature search was conducted using multiple databases comprising of PubMed, Scopus, Google Scholar, and Cochrane electronic databases with keywords including microbiome, microbiota, carcinogenesis, tumorigenesis, and immunosuppression. Current and the past literature has pointed out the role of microorganisms in oncogenesis. It may be put forth that both the commensal and pathogenic strains of oral microbiome play an undeniably conspicuous role in carcinogenesis at different body sites.

Effect of retinoic acid on type I diabetes: Streptozotocin-induced rat model

To evaluate the effect of all trans retinoic acid [atRA] on differentiation/transdifferentiation of pancreatic duct/acinar cells into insulin secreting beta-cells in diabetic rats. 64 adult male rats divided into four groups. Normal control, diabetic control, atRA-I: diabetic rats treated with atRA [0.1 mg/kg/day, subcutaneously] and atRA-II: diabetic rats treated with atRA [2.5 mg/kg/day, subcutaneously] for 1, 2 and 4 weeks. The levels of glucose and insulin were measured. Histopathological, immunohistochemical examination of pancreas and RT-PCR of insulin mRNA were done. atRA led to an improvement in the level of glucose and insulin in both doses and at the different time points when compared with diabetic control. Histopathological examination of the pancreas revealed that atRA in both doses and at different time points nearly restored the normal appearance of the islets of Langerhans. Interestingly, some islets of Langerhans were found closely related to the interlobular ducts and the acinar epithelium. Mitotic figures were observed in the epithelium of the interlobular ducts and acinar cells and inside the islets of Langerhans especially with high dose. The immunohistochemical revealed strong insulin-immunoreactivity in the cytoplasm of the beta-cells and in the cytoplasm of the isolated cells which are closely related to the acini. Also, insulin mRNA expression showed dense band illumination similar to normal control. Retinoic acid may induced significant increase in insulin level and its mRNA, decrease glucose level and increased beta-cells regeneration through increased pancreatic duct and/or acinar cells differentian/transdifferentiation and increased proliferation of fbeta-cells in diabetic rats

Cytokines and growth factors in children with burns, relation to burn surface area, sepsis and survival

Burn is a unique injury which is not only devastating for the patients but also puts a great burden on the society by consuming enormous health care resources. Despite improvements in burn wound care and treatment, understanding the role of pro-inflammatory, anti-inflamatory cytokines as well as the mechanisms responsible for the healing process remains to be clarified. Although leptin is regarded as a circulating hormone, it can exert direct effect on T cells and monocytes, causing the release of cytokines. It may induce angiogenesis or influence angiogenic factors. The aim of the present work is to determine serum levels of leptin, TNFalpha, IL-6, TGFalpha, and bFGF, PCT and CRP in a group of children with thermal burn and to determine the changes in these parameters in relation to the duration of hospital stay, the presence of infection and the total burn surface area. The study included 42 children with burns. They were 22 males and 20 females. Their ages ranged from 2 months to 7 years. The study also included 26 age matched controls. Beside full clinical assessment including assessment of total burn surface area [TBSA] and the presence or absence of sepsis, all the cases and controls had the following investigations done: CBC, C-reactive protein [CRP], IL-6, TNFalpha, procalcitonin [PCT], serum leptin, basic fibroblast growth factor [bFGF], and transforming growth factor alpha [TGFalpha]. The fatality rate in this study was 28.6%. Burn cases as a whole showed significantly higher values of WBC, CRP, PCT, TNFalpha, IL-6, leptin, bFGF, and TGFalpha than controls. Cases with sepsis showed significantly higher values of WBC, CRP, PCT, TNFalpha and lL-6 than cases without sepsis. They showed significantly lower values of TGFalpha than cases without sepsis. Patients with larger TBSA [>30%] showed significantly higher levels of WBC, CRP, PCT, TNFalpha and lL-6 and leptin than cases with smaller TBSA. They showed significantly lower levels of bFGF, and TGFa than cases with smaller TBSA. Nonsurvivors showed significantly higher levels of WBC, CRP, PCT, TNFalpha and IL-6 than survivors. They showed significantly lower levels of leptin, bFGF, and TGFalpha than survivors. Correlation studies showed significant positive correlation between TBSA and each of IL-6, TNFalpha and leptin. Cytokines and leptin were increased in severe burn cases, cases associated with sepsis as well as in fatal cases. bFGF and TGFalpha levels were lower in severe cases. This may point to the impaired healing and to the poor prognosis in such cases. Recommendations: It is highly recommended to monitor immunologic parameters such as PCT and/or IL-6 for early detection of infectious complications following thermal injury. Leptin can be regarded as a novel treatment modality to diminish burn induced inflammation, to reduce post burn immune dysfunction and to enhance burn healing

Serum antioxidant and pro-oxidant trace elements: relationship with oxidative stress in children with chronic renal failure on regular hemodialysis

There is a good evidence indicating that uremia, in general, is associated with enhanced oxidative stress and treatment of uremic patients with hemodialysis [HD] or peritoneal dialysis [PD] has been suggested to particularly contribute to oxidative stress and reduced antioxidant levels in those patients. Also uremic patients have abnormalities in trace elements which maybe caused by the uremia itself and/or enhanced or modified by the dialysis procedures. The aim of this study was to evaluate the oxidative stress imbalance and its relationship to the trace elements in children with chronic renal failure [CRF] on regular HD. This study was conducted on 36 children with CRF on regular HD and in 25 age and sex matched normal control children. Thiobarbituric acid [TBARS], total antioxidant [TAO], and hydrogen peroxide [H[2] O[2]] were measured by colorimetric assays. Trace elements [selenium [Se[+2]], zinc[zn[+2]], copper [Cu[+2]], manganese [Mn[+2]], lead [Pb[+2]] and cadmium [Cd[+2]] were measured by atom absorption/flame emission spectrophotometry. The results showed that the serum concentrations of TBARS, H[2]O[2], Cd and Pb were significantly higher in the studied cases [2.498 +/- 0.29, 2.967 +/- 0.414, 21.74 +/- 2.37 and 38.01 +/- 4.18 respectively] than in the controls [1.649 +/- 0.093, 0.311 +/- 0.032, 5.83 +/- 0.68 and 12.67 +/- 0.85 respectively] P<0.05 and P<0.001 for the others. The serum concentration of TAO, selenium, zinc and copper were significantly lower in the studied cases [1.379 +/- 0.017, 2.411 +/- 0.138, 91.07 +/- 2.979 and 84.89 +/- 3.145 respectively] than in the controls [2.049 +/- 0.014, 4.012 +/- 0.203, 128.7 +/- 4.924 and 128.7 +/- 3.904 respectively] [P<0.001 for each]. A significantly positive correlations were found between serum levels of cadmium and TBARS and between serum levels of selenium and TAO [r=0.359 P<0.05, and r=0.398, P<0.05 respectively]. Also a significant negative correlation was found between serum levels of zinc and serum level of TBARS [r=-0.392 P<0.05]. Our data suggest an enhanced oxidative stress and significant changes in trace elements in end stage renal disease [ESRD] patients undergoing HD. Also there is a significant relationship between the oxygen stress imbalance and the changes in the trace elements in these patients

cardio-pulmonary study on thalassemic children: relation to oxidant antioxidant balance and iron overload

beta-Thalassemia major is a common inherited disorder of hemoglobin synthesis in which iron overloading from regular blood transfusions results in organ dysfunction. Heart and liver dysfunction in thalassemia have been extensively-studied owing to their early effect on survival. Pulmonary dysfunction on the other hand is one of the least understood complications of beta-thalassemia major and represents one of the least studied complications in thalassemic patients. The aim of this study was to define the spirometric pattern and the possible causes of lung impairment in thalassemic patients. The study included 39 thalassemic patients [19 females and 20 males], with an age range from 8 to 16 years. Eighteen controls of matched age and sex were included in the study. A complete history was taken and a thorough physical examination was performed. In addition, the following investigations were done before blood trans fusion: Hb, serum ferritin level, AST, ALT, erythrocytic thiobarbituric acid reactive substance [TBARS], super oxide dysmutase [SOD]'glutathione peroxidase [GPx], serum TBARS, SOD, glutathione [GSH], and vitamins A, C and E. Echocardiography was also done for all patients, the day before blood transfusion. Pulmonary function testing and arterial blood gases were performed prior to blood transfusion and 24 hours after blood transfusion. Restrictive lung pattern was predominant in beta-thalassemia major patients. This was manifested by a significantly lower FVC and a significantly higher FEV1/FVC in the studied patients than the controls. FVC carried significant negative correlation with ferritin. Patients had significantly higher values of TBARS and significantly lower values of serum SOD, GSH and the erythrocytic SOD and GPx and vitamins [E, A and C]. FVC carried significantly negative correlation with TBARS and significantly positive correlations with erythrocytic SOD, GPx, vitamins A and E. LVESD and LVEDD were significantly higher in the studied patients than the controls and both correlated negatively with FVC. EF, FS and PAT were significantly lower in the studied patients. EF and FAC correlated positively with FVC. L VESD and LVEDD correlated positively with ferritin and TBARS but negatively with GPx. restrictive lung disease was found to be the predominant pulmonary dysfunction in thalassemia major patients. This seems to be related to ferritin level, and might reflect the role of iron deposition and accumulation in the pathogenesis of pulmonary disease in thalassemia major. The restrictive pattern may also result from excess oxidative damage to the alveolar tissue or from cardiac changes that occurred in these patients. Accurate and early evaluation as well as follow up of pulmonary function and of bronchial reactivity is advisable for all patients with TM. Initial and follow up of cardiac performance in patients with thalassemia major is also important as it has a great impact on pulmonary functions in these patients. An ultimate goal in the management of thalassemia major is to design and try a combination of oral antioxidants and oral iron chelator to achieve good patient's compliance with the ease of administration for such patients who are living on repeated blood transfusion and hospital admission

study on hemolytic uremic syndrome [HUS] among hospitalized children with shiga toxin producing E. coli 0157:H7 infection

Diarrhea continues to be a major cause of childhood mortality and morbidity in developing countries. Although mortality from diarrheal diseases is declining, morbidity is not. The hemolytic uremic syndrome [HUS] has been reported to be a common complication in bloody diarrhea particularly that caused by entero-hemorrhagic E. coli, a subset of E. coli that produces potent cytotoxins known as shiga like toxins [STx] and the organism is therefore called shiga toxin producing E. coli [STEC]. The exact mechanism responsible for HUS, however, remains speculative. Endothelial injury, acute inflammatory response to STEC or its STx has been blamed. The aim of this work is to study the percentage frequency of STEC infection and the percentage frequency of HUS in a group of hospitalized diarrheal children with and without blood in stools. We also aim to study some of the inflammatory cytokines [TNF alpha, IL-8], vascular endothelial factors such as Endothelin-1 [Et-1] and nitric oxide [NO], and the angiogenic peptide released in response to endothelial injury [bFGF] in these cases. The study included 200 patients less than 5 years of age having acute diarrhea. Cases with protozoal infection were excluded from the study. All cases besides having thorough clinical history and examination, had stool culture and serotying of STEC 0157:H7 on admission. For all cases renal function tests, full blood count and smear, serum sodium and potassium levels were measured. For cases with proven STEC 0157:H7 infection, TNf alpha, IL-8, Et1, NO and bFGF were determined. The percentage frequency of STEC 0157:H7 was 43%, of them 40% were in cases with blood in stools. The percentage frequency of HUS was 35%; all were cases with bloody diarrhea and STEC 0157: H7 infection. The percentage frequency of antibiotic administration among all cases was 67%. However among case with STEC infection that developed HUS 71% received antibiotics. Cases with STEC associated -HUS showed significantly younger mean age with significantly longer mean duration of hospitalization than the rest of case with STEC infection without HUS. They showed significantly higher percentage frequency of: fever >/= 38°C, vomiting, hematuria, anuria, hypertension, CNS complications [seizures, encephalopathy, intractranial hemorrhage and brain infarction], and deaths than the rest of the cases. They also showed significantly lower mean sodium, hemoglobin, platelets and nitric oxide values and significdantly higher mean potassium, urea, creatinine, WBC count, PMNL, and reticulocytic count, TNF alpha, IL-8, Et-1, and bFGF correlated positively with creatinine and WBC but negatively with platelets. NO correlated negatively with TNF alpha, IL-8, Et-1, and bFGF. STEC infection is higher among the studied cases, pointing to the role of cross transmission among hospitalized patients. Hemolytic uremic syndrome complicates 35% of these cases. Diarrheal cases with HUS were associated with more serious complications such as hypertension, encephalopathy, and intracranial hemorrhage. These complications may cause permanent disability and sometimes have fatal outcome. Furthermore the duration of hospital stay was considerably longer than cases without HUS. In STEC associated HUS with these complications, the prognosis is usually grave than in the absence of such complications. Bad prognostic signs of HUS include: younger age, leukocytosis >14,000, prolonged anuria and oliguria, persistent thrombocytopenia, as well as the presence of CNS complications

study of some biochemical parameters of pulmonary hypertension in children with congenital and rheumatic heart disease

The study included 36 cases with congenital heart disease [CHD] all of them had left to right shunt [17 cases of them had pulmonary hypertension [PHT], 30 cases with valvular rheumatic heart disease [RHD] [15 of whom had PHT]. Ten healthy normal age-matched children were taken as control for each group. Full history and physical examination, pulse oximetry, standard 13-lead ECG and detailed echocardiographic examination were done for every patient and control case. Chest radiograph posterantrior view in erect position was done for all patients. Erythrocytic sedimentation rate, C-reactive rotein and antistreptolysin-O titer were done for patients with RHD. All cases and controls had the following done: plasma level of endothelin-1 [ET-1], angiotesin-II [ANG-II], nitric oxide [NO] and serum level of angiotesin-converting enzyme [ACE] activity. The mean peak pulmonary pressure [PP] in patients having CHD and PHT was 54.35 +/- 9.69 mm Hg, while it was 61.73 +/- 11.55 mm Hg in those with RHD and RHT. The mean peak PP in the group of patients having CHD without PHT was 22.64 +/- 4.11 mm Hg. It was significantly higher than in those with RHD without PHT [9.41 +/- 1.98 mm Hg, P<0.05] and than controls [4.12 +/- 1.25, P<0.01]. It was observed that the mean levels of ET-1, NO, ANG-II and ACE were significantly higher in all cases with CHD [3.42 +/- 0.77, 77.21 +/- 29.14, 81.27 +/- 37.3, 107.2 +/- 47.65, P<0.001], cases with PHT [3.76 +/- 0.81, 94.1 +/- 21.1, 101.4 +/- 33.8, 136.2 +/- 37.9, P<0.001] OR without PHT [2.92 +/- 0.6,61.36 +/- 27.5, 63.28 +/- 16.5, 85.36 +/- 22.6, P<0.5 and 0.01] than in their controls [1.86 +/- 0.6, 34.07 +/- 10.7, 19.15 +/- 10.9, 54.1 +/- 32.1]. It was observed that the mean level of ET-1, NO, ANG-II and ACE were significantly higher in cases with CHD with PHT than in those without PHT [p<0.05 for each]. In the group of patients with RHD, it was observed that the mean levels of ET-1, NO, ANG-II and ACE were significantly higher in all cases [3.89 +/- 1.4, 78.46 +/- 59, 70.35 +/- 37.4, P<0.01 and 0.001] and cases with PHT [4.9 +/- 1.0, 100.5 +/- 32, 95.7 +/- 36.8, 121 +/- 40.9, P <0.001] than in controls [1.55 +/- 0.5, 33.47 +/- 13.0, 22.68 +/- 11.1, 53.27 +/- 32.4]. It was also observed that the mean levels of ET-1, NO, ANG-II and ACE were significantly higher in cases with than in those without PHT [2.6 +/- 0.8, 56.5 +/- 18.0, 44.96 +/- 12.7, 63.3 +/- 37] [P<0.01]. It was observed that the mean levels of ET-1, ANG-II and ACE were significantly higher in cases with CHD having heart failure [3.8 +/- 0.73, 106.8 +/- 50.37, 155.3 +/- 65.66] than those without heart failure [3.26 +/- 0.7, 69.88 +/- 25.1, 91.85 +/- 32.8], P<0.05 and 0.001. There was statistically significant positive correlation between PP in all the studied patients and serum level of ET-1, NO, ANG-II and ACE [P<0.001]. A significant positive corrlation was found between serum level of ET-1 and NO in all the studied cases [P<0.05]. A significant positive correlation was also found between serum level of ANG-II and ACE in all the studied cases [P<0.03]. ET-1 and NO production is increased in cases with PHT secondary to CHD with left to right shunt and to RHD and its production correlates with the level of PP. It could be also concluded that the level of ANG-II and ACE activity is increased in cases with PHT secondary to CHD with left to right shunt and to RHD and its production correlates with the level of PP. The use of NO, NO donors, prostacyclin and ET-1 antagonists should be considered in the management of pulmonary hypertension secondary to hyperkinetic arterial PHT due to CHD with left to right shunt and in the management of venous pulmonary hypertension secondary to RHD. The long-term effect of such drugs on the pathological process in such cases should be studied. Still early intervention in cases with hyperkinetic arterial PHT due to CHD with left to right shunt before the end of the first year of life is highly recommended. It may be also suggested that the use of ACE inhibitors could be useful to prevent the effects of ANG-II on the pulmonary vascular pathology

Dyslipidemia, oxidative stress and cardiac dysfunction in children with chronic renal failure: effects of l-carnitine supplementation

Secondary carnitine deficiency may develop in chronic renal failure [CRF] patients undergoing long-term hemodialysis [HD], with a resulting higher incidence of cardiovascular diseases, dyslipidemia and oxidative stress. We studied the efficacy of 12 months of L-carnitine supplementation on the amelioration of dyslipidemia, oxidative stress and cardiac dysfunction in 24 CRF children undergoing long-term HD compared with 24 age- and sex-matched controls. Plasma samples were analyzed spectrophotometerically before and after dialysis sessions and after 2-month supplementation with oral L-carnitine [50 mg/kg/day] for free carnitine [FC], the lipid profile, and oxidative stress markers. Echocardiography the day following dialysis measured cardiac diameters, wall thicknesses, left ventricular mass index [MI], end diastole and systole volume indices and functions. The pre-dialysis FC concentration was substantially lower than controls and decreased significantly at the end of the dialysis session. Pre- and post-dialysis plasma levels of free fatty acids [FFAs], trigyleride [TG], total cholesterol [TC] and oxidative stress markers significantly increased while high-density lipoprotein cholesterol [HDL-C] and phospholipids significantly decreased compared to controls. Echocardiography detected a significant increase in cardiac diameters and thickness, and systolic and diastolic cardiac dysfunction. After L-carnitine supplementation, plasma levels of FC increased to normal levels. FFAs, TC and HDL-C returned to control levels while TG, phospholipids, and the oxidative stress markers decreased but remained significantly higher than controls. There was a significant decrease in cardiac diameters and an increase in left ventricular diastolic function [E/A ratio], but no correlation between FC levels and echocardiographic parameters. Pre-dialysis, post-dialysis and after treatment, plasma FC level showed a significant positive correlation with HDL-C and phospholipids and a significant negative correlation with each of oxidative stress markers, FFAs, TG and TC. On the other hand, FFAs showed a significant positive correlation with TG, TC, DC, NO and a significant negative correlation with HDL-C and phospholipids. This study demonstrates that CRF children under regular HD suffer from a decrease in the level of plasma FC, dyslipidemia, oxidative stress, and an increase in cardiac diameters and thickness with impairment of cardiac functions. Oral L-carnitine supplementation at a dose of 50 mg/kg for 2 months can increase plasma FC level, improve dyslipidemia, decrease oxidative stress with reduction of cardiac diameters and increase in diastolic function

Diagnostic value of serum procalcitonin as a marker of bacterial infection in cirrhotic patients with fever

This study was done to evaluate the value of procalcitonin in the diagnosis of the infectious etiology of fever in patients with liver cirrhosis. The study included 41 patients with liver cirrhosis of different grades of severity, 31 of them presented by fever and 10 without fever [considered as a control group]. After thorough investigations, the focal sites of infection were localized in 20 patients [respiratory tract infection in 10 patients, urinary tract infection in 4 cases and spontaneous bacterial peritonitis in 6 cases] and no specific site was detected in 11 patients. Blood culture was positive only in four cases and all were Gram -ve bacilli. A highly significant difference in the mean serum level of procalcitonin [PCT] between cirrhotic patients with fever and those without fever was found. The same was true for serum C-reactive protein [CRP], but no statistical difference was found between the two groups regarding leucocytosis. PCT showed 100% sensitivity and 80% specificity in the diagnosis of infectious etiology of fever in patients with liver cirrhosis. It was concluded that PCT has a diagnostic value in differentiating the infectious etiology of fever in patients with liver cirrhosis and fever. This allows to start early treatment in those immunocompromised patients

Impact of oxidative stress and smoking on muscle fatigue markers during a single bout of exercise

In this study, 18 male well-trained physical education faculty senior students were randomly selected and grouped into smoker [5 active + 4 passive] and non-smoker [9] student groups. Plasma was collected immediately before and after a single bout of endurance track running exercise. A selected number of least invasive plasma indices of muscle fatigue [lactate and activity of lactate dehydrogenase, LDH, and xanthine oxidase, XO]. Oxidative stress [thiobarbituric acid reactive substances [TBARS], nitric oxide [NO], total iron and [Fe2+]], antioxidation [total antioxidant activity [TAOA], urate, ascorbate total zinc [Zn2+] and selenium [Se2+]] and superoxide dismutase activity [SOD] were measured using atomic absorption flame photometric and colorimetric techniques. Smoking index was calculated and plasma cotinine, the endogenous nicotine metabolic indicator, was measured using ELISA technique. Exercise induced a significant increase in muscle fatigue and peroxidative indices [lactate, LDH, XO, TBARS, NO and Fe2+] and a significant decrease in Se2+, Zn2+ and ascorbate. There was a significant increase in TAOA and SOD and a nonsignificant increase in urate in the two groups. Smokers showed significantly higher basal peroxidative and lower antioxidation indices compared with nonsmokers, a picture that was exacerbated post-exercise. These changes could not be reflected significantly on the indices of exercise and cardiorespiratory endurance