Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

/pdf/therapeutic-roles-of-curcumin-lessons-learned-from-clinical-5zsv15a4lb.pdf

Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Risk factors play an important role in an individual's response to periodontal infection. Identification of these risk factors helps to target patients for prevention and treatment, with modification of risk factors critical to the control of periodontal disease. Shifts in our understanding of periodontal disease prevalence, and advances in scientific methodology and statistical analysis in the last few decades, have allowed identification of several major systemic risk factors for periodontal disease. The first change in our thinking was the understanding that periodontal disease is not universal, but that severe forms are found only in a portion of the adult population who show abnormal susceptibility. Analysis of risk factors and the ability to statistically adjust and stratify populations to eliminate the effects of confounding factors have allowed identification of independent risk factors. These independent but modifiable, risk factors for periodontal disease include lifestyle factors, such as smoking and alcohol consumption. They also include diseases and unhealthy conditions such as diabetes mellitus, obesity, metabolic syndrome, osteoporosis, and low dietary calcium and vitamin D. These risk factors are modifiable and their management is a major component of the contemporary care of many periodontal patients. Genetic factors also play a role in periodontal disease and allow one to target individuals for prevention and early detection. The role of genetic factors in aggressive periodontitis is clear. However, although genetic factors (i.e., specific genes) are strongly suspected to have an association with chronic adult periodontitis, there is as yet no clear evidence for this in the general population. It is important to pursue efforts to identify genetic factors associated with chronic periodontitis because such factors have potential in identifying patients who have a high susceptibility for development of this disease. Many of the systemic risk factors for periodontal disease, such as smoking, diabetes and obesity, and osteoporosis in postmenopausal women, are relatively common and can be expected to affect most patients with periodontal disease seen in clinics and dental practices. Hence, risk factor identification and management has become a key component of care for periodontal patients.

Risk factors for periodontal disease.

Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care.

Prevalence of periodontal disease, its association with systemic diseases and prevention.

Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

/pdf/measurement-and-clinical-significance-of-biomarkers-of-4b5iqooayx.pdf

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/odi.12446

Vitamin C: the known and the unknown and Goldilocks.

Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage.

/pdf/possible-action-mechanism-for-curcumin-in-pre-cancerous-1ewln8pbgw.pdf

Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress

Background: Some cross-sectional and longitudinal studies attempted to link periodontitis with stress. To our knowledge, only one small study was published on the mechanism by which stress may influence periodontal diseases, suggesting behavioral and physiologic mechanisms and investigating the role of inflammation as a potential mediator. The present study is planned to explore the associations among periodontal disease, psychologic factors, and salivary markers of stress, psychoneuroimmunologic variables, and health behaviors.Methods: One hundred periodontitis patients were selected, and participants provided information on general health, chronic stress, and demographics. Stress markers (choromogranin A, cortisol, α-amylase, and β-endorphin) were measured from saliva. A dentist assessed the presence of dental plaque on lingual and buccal surfaces, the gingival index, and the number of remaining teeth with periodontal disease.Results: Stress and salivary stress markers were significantly correlated with...

Salivary Stress Markers, Stress, and Periodontitis: A Pilot Study

The objective of the study was to conduct a systematic review of the literature assessing potential salivary biomarkers of oral cancer and pre-cancer and discuss emerging issues and challenges in relation to oral cancer and pre-cancer diagnostics. Search for articles involved the Medline, PubMed, and EMBASE. Specific terms were used from January 1995 to March 2017 by three experts. This search collected 270 articles, of which 105 articles such as reviews, case reports, news, letter to editor, etc. in first round and 117 articles such as publications in other languages than English, non-human studies, etc. were excluded. The remaining 48 articles considered analyzing whole saliva as well as specific gland saliva. Thirty-one studies considered oral stimuli such as eating, drinking, and oral hygiene practices for varied periods of time prior to sample collection. The time of collection of saliva was morning in most studies, but the exact time of collection was not mentioned. Three studies showed to have evaluated the whole saliva without centrifugation. Two-dimensional gel electrophoresis and tandem mass spectrometry were the most commonly used methods. Most of the potential salivary biomarkers of oral cancer are salivary proteins. Combination approach of salivary biomarkers could be used as screening tool to improve early detection and diagnostic precision of oral pre-cancer and cancer. The current findings are of importance for clinicians and researchers to mitigate the challenges in salivary-based diagnosis of oral cancer and to evaluate reliable, specific, and sensitive salivary biomarkers for oral pre-cancer and cancer diagnosis.

Salivary biomarkers for oral cancer and pre-cancer screening: a review.

Objectives: The objective of this study was to identify salivary and serum concentrations of interleukin (IL)-8, IL-6, and tumor necrosis factor alpha (TNF-α) in patients with oral lichen planus, oral leukoplakia, oral submucous fi brosis, and healthy controls. Materials and Methods: Patients selected included 54 oral lichen planus (41 to 65 years), 50 oral leukoplakia (42 to 65 years), 51 oral submucous fibrosis (41 to 65 years), and 50 healthy controls (42 to 65 years). Oral lichen planus, oral leukoplakia, and oral submucous fi brosis cases were diagnosed using histopathological analysis. Salivary and serum cytokine concentrations were measured using enzyme-linked immunoassay kits in all subjects. Results: The levels of serum and salivary TNF-α, IL-6, and IL-8 were statistically signifi cantly increased in oral leukoplakia, submucous fi brosis, and lichen planus in contrast to normal healthy subjects (P＜0.05). Serum and salivary correlation analysis revealed strong and highly signifi cant correlations for TNF-α, IL-6, and IL-8 in all groups (r=0.72-0.82, P＜0.05). Conclusion: Salivary and serum cytokines were also elevated when analyzed in oral precancerous lesions. Thus, salivary and serum IL-8, IL-6, and TNF-α levels might act as diagnostic markers for detection of oral precancer.

/pdf/proinflammatory-cytokine-levels-in-oral-lichen-planus-oral-19s0vfv0f5.pdf

Proinflammatory cytokine levels in oral lichen planus, oral leukoplakia, and oral submucous fibrosis.

Tongue cancer is amongst the most common and fatal types of cancers in the world The abnormalities in purine metabolism are characteristic features of many human tumors Little is known about the correlation between the activities of key enzymes of purine nucleotide pathway and clinical indicators of tongue cancer invasiveness and aggressiveness Fifty patients (M: F 25:25; mean age: 556 years (range 45-60; SD 18)) with diagnosed squamous cell carcinoma of the tongue (test group) and 30 normal subjects (M: F 15:15) without any systemic disease (control group) were recruited after obtaining informed consent All patients were staged by the TNM classification Salivary adenosine deaminase (ADA) activity was assessed in cancerous patients (test group) and normal healthy subjects (control group) Statistically significant differences between test and control groups were observed in salivary ADA (P < 0001) Furthermore, serum ADA levels significantly increased as the disease stage progressed from stage I to stage III of squamous cell carcinoma of the tongue in both genders (P < 0001) Salivary ADA might be used as a diagnostic tool for early detection of squamous cell carcinoma of tongue

Adenosine deaminase in saliva as a diagnostic marker of squamous cell carcinoma of tongue.

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