Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation.

BACKGROUND: Curcumin is a major active principle of Curcuma longa. There are more than 1700 citations in the Medline, reflecting various biological effects of curcumin. Most of these biological activities are associated with the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that include growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that target the cancer and inflammation. METHODOLOGY: In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules. RESULTS: Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed. CONCLUSION: The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.

Impact of Gene-Environment Interactions on Cancer Development.

Several epidemiological and experimental studies have demonstrated that many human diseases are not only caused by specific genetic and environmental factors but also by gene-environment interactions. Although it has been widely reported that genetic polymorphisms play a critical role in human susceptibility to cancer and other chronic disease conditions, many single nucleotide polymorphisms (SNPs) are caused by somatic mutations resulting from human exposure to environmental stressors. Scientific evidence suggests that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Research has also pointed out that the interactions of environmental factors with specific allelic variants highly modulate the susceptibility to diseases. Hence, many scientific discoveries on gene-environment interactions have elucidated the impact of their combined effect on the incidence and/or prevalence rate of human diseases. In this review, we provide an overview of the nature of gene-environment interactions, and discuss their role in human cancers, with special emphases on lung, colorectal, bladder, breast, ovarian, and prostate cancers.

A New Model Applied for Evaluating a Rhenium-diselenium Drug: Breast Cancer Cells Stimulated by Cytokines Induced from Polynuclear Cells by LPS.

BACKGROUND/AIM: New anticancer drugs are usually tested on cancer cells in culture in a standard medium. We stimulated immune polynuclear cells by lipopolysaccharides to obtain an enriched medium (EM) containing inflammatory cytokines more closely reflecting the tumor microenvironment and tested a rhenium-diselenium (Re-diSe) drug in this new model. Concentrations of cytokines were compared with a control medium (CM). MATERIALS AND METHODS: Human-derived breast cancer cells were grown in culture either in CM or EM with or without Re-diSe. Assays of tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), intereukin 1 beta (IL1ß), transforming growth factor-beta (TGFß), insulin growth factor 1 (IGF1) and vascular epidermal growth factor A (VEGFA) were performed by enzyme-linked immunosorbent assays. The production of reactive oxygen species (ROS) was determined by 2,7-dichlorofluorescein test. The cell growth was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests. RESULTS: Concentrations of TNFα, IL6 and Il1ß were observed to be significantly higher in EM than in CM. There was no difference for TGFß, IGF1 and VEGFA. The cells were sensitive to Re-diSe, with reduced concentrations of TGFß, IGF1, VEGFA and ROS, but the half-maximal inhibitory concentration was significantly higher in EM than in CM. CONCLUSION: The efficacy of the Re-diSe drug was confirmed in this model of aggressive cancer.

Comparative Assessment of Cephalometric and Tympanometric Readings in Down Syndrome.

Aim  The purpose of this study was to conduct a comparative assessment of the various cephalometric and auditory parameters between patients with Down syndrome (DS) and healthy controls. Methods The cephalometric and auditory parameters were divided among 50 participants into two equal sets, DS (n = 25) and controls (n=25), and assessed. While a standard cephalometric analysis was conducted to measure the hard tissue parameters, tympanometry was used to assess the audiological parameters. Results The values of the linear and angular cephalometric parameters of the DS group were found to be lower than the controls. All the controls recorded type A tympanogram while the DS group recorded type A, B, and C tympanograms. A significant relationship was observed in the cephalometric readings - eustachian tube (ET) length, posterior upper facial height (PUFH) length, sella (s)-basion (ba)-palatal length (PL), and s-ba-ET angles - among the subjects who presented with type B or C tympanogram in comparison to those with type A. Conclusion  Tympanometry, a highly sensitive and relatively simple test to assess audiological parameters, has a significant relationship with a number of cephalometric indicators of growth and development. A deviation from the normal tympanometric readings can be used as an early indicator of the impending craniometric aberrations and handicap. This can be used as an effective tool for early intervention in cases of DS. Patients who have recorded abnormal tympanograms on multiple occasions over a period of six months can be subjected to a further cephalometric analysis.

Oral Health and Feto-maternal Outcomes in the Context of Sustainable Development Goals.

The linkages of oral health with the holistic health of an individual are now well-established. Nevertheless, marginalizing oral health continues to pose a challenge in the public health scenario globally and especially in developing countries. Maternal and fetal health have been regarded as pivotal yardsticks of development in all civil societies. The oral cavity acts as a route of entry for various microorganisms into the body and oral lesions are easily detectable. Thus, early intervention is possible and morbidity in the vulnerable populations can be reduced.

Oral Health Status and Fertility Treatment Including IVF.

Oral health is extremely important for the general wellbeing of the individual. From a number of research articles, it is established that there is a definitive connection between periodontal health and many systemic diseases, like type II diabetes, cardiovascular diseases and even preterm labor and low birth weight of babies. The significant rate of failure in the treatment of infertility and IVF (in vitro fertilization) even with multiple advancements in the last decade has made scientist take interest in newer parameters of health, an important one among them being periodontal health. From the limited number of studies available on the relationship between periodontitis and reproductive health, it can be inferred that periodontitis can act as a focus of infection leading to bacteremia which can lead to complications in conceiving naturally or through IVF in women. A limited number of studies have also reported an association between male factor infertility (MFI) and dental health status of men. Although more research is needed to understand and explore this connection, this article reviews the current literature available linking poor oral health to infertility and poor outcomes of IVF.

Petroleum Carcinogenicity and Aerodigestive Tract: In Context of Developing Nations.

Head and neck cancers from a diverse group of neoplasms, the occurrence of which can be attributed to habitual tobacco use, race, alcohol consumption, ultraviolet (UV) exposure, occupational exposure, viruses, and diet. The surging incidence rates reflect the prevalence of risk factors such as tobacco use (smoked and smokeless), betel nut chewing, urbanization and issues relating to urban air quality. Urbanization and development have catalyzed a multifold rise in levels of pollution in metropolitan cities. Ever-increasing consumption of fuels to meet demands of the growing population coupled with industrial activity has adversely affected the air quality, especially in developing countries. The cause most neglected in risk assessment of aerodigestive tract cancer research is that from petroleum exposure. The global issue of petroleum carcinogenicity has assumed high proportions. Polycyclic aromatic hydrocarbons and heavy metals are essential constituents of total petroleum hydrocarbons which infiltrate into the environment and are recognized worldwide as priority pollutants because of their toxicity and carcinogenicity. High levels of sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, ammonia and particulate matter PM10  has skyrocketed aerodigestive tract diseases especially carcinomas. The identification of specific biomarkers and role of metal ions in aerodigestive tract cancers will indicate the molecular basis of disease to provide quality care for patients confronting new threats from climate-sensitive pathologies. There is an urgent need to evaluate existing public health infrastructure so as to take ameliorative and adaptive measures.

Trace elements (copper, zinc, selenium and molybdenum) as markers in oral sub mucous fibrosis and oral squamous cell carcinoma.

Oral cancer is a major cause of cancer morbidity and mortality worldwide and is prevalent in most areas where tobacco related practices are observed. Essential elements play a role in many biochemical reactions as a micro-source and there is growing evidence that their concentrations are altered on the onset and progress of malignant disease. In this study the levels of copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo) in serum of patients with oral sub mucous fibrosis (OSMF) (n = 30) and oral squamous cell carcinoma (OSCC) (n = 30); were determined and the alterations of these critical parameters were analyzed in comparison with controls (n = 30) to identify predictors amongst these parameters for disease occurrence and progression. The serum Cu and Zn were established using Flame Atomic Absorption Spectrometry. Serum estimation of Se and Mo was done by graphite furnace atomic absorption spectrometry (GFAAS). Data analysis revealed a marked, progressive and significant increase in Cu levels in precancer (OSMF) and cancer (OSCC) groups as compared to the normal group. The level of Zn in serum was slightly elevated in OSMF and OSCC though not statistically significant. Cu/Zn ratio was slightly but not significantly elevated. Serum levels of Se and Mo were significantly decreased in the precancer and cancer groups as compared to the normals.

The interaction between tobacco use and oral health among tribes in central India.

BACKGROUND: A study was undertaken to evaluate the effect of tobacco related practices on oral health of tribes in Central India. The use of smokeless tobacco, gutkha & associated products is on the rise amongst the younger generation making oral precancer & cancer a public health concern. METHODOLOGY: A pioneering study was conducted to evaluate the tobacco related practices amongst tribes and its impact on oral health. The study included 411 tribals of the Baiga group. Guided dialogue techniques and proforma based evaluation formed a part of the study. RESULT: 53.04% of individuals between 21 to 40yrs are addicted to deleterious habits. There is a marked consumption (72%) of tobacco & associated products among the geriatric population (60 yrs & above).Insecure livelihoods, malnutrition & increased stress levels contribute to the stark increase of addiction of tobacco related practices. CONCLUSION: The healthcare infrastructure needs to be upgraded to meet the demands of changing disease profile amongst the vulnerable population. Assessment of impact of disease on existing public health would enable formulation of adaptive measures and suggestions for amelioration.

Artificial intelligence: contemporary applications and future compass.

The clinical use of information technology in the dental profession has increased substantially in the past 10 to 20 years. In most developing countries an insufficiency of medical and dental specialists has increased the mortality of patients suffering from various diseases. Employing technology, especially artificial intelligence technology, in medical and dental application could reduce cost, time, human expertise and medical error. This approach has the potential to revolutionise the dental public health scenario in developing countries. Clinical decision support systems (CDSS) are computer programs that are designed to provide expert support for health professionals. The applications in dental sciences vary from dental emergencies to differential diagnosis of orofacial pain, radiographic interpretations, analysis of facial growth in orthodontia to prosthetic dentistry. However, despite the recognised need for CDSS, the implementation of these systems has been limited and slow. This can be attributed to lack of formal evaluation of the systems, challenges in developing standard representations, cost and practitioner scepticism about the value and feasibility of CDSS. Increasing public awareness of safety and quality has accelerated the adoption of generic knowledge based CDSS. Information technology applications for dental practice continue to develop rapidly and will hopefully contribute to reduce the morbidity and mortality of oral and maxillofacial diseases and in turn impact patient care.

Immunological and biochemical markers in oral carcinogenesis: the public health perspective.

Oral health is an integral component of general health and well being and a basic human right. Dental public health is probably the most challenging specialty of dentistry. Because of the lack of adequate resources among other factors, many people are likely to suffer from dental diseases. Despite great improvements in the oral health status of populations across the world, the burden and impact of dental diseases are still high. This is particularly true among underprivileged groups in both developed and developing communities. Oral diseases and conditions, including oral cancer, oral manifestations of HIV/AIDS, dental trauma, craniofacial anomalies, and noma, all have broad impacts on health and well-being. Oral cancer, the sixth most common cancer worldwide continues to be most prevalent cancer related to the consumption of tobacco, alcohol and other carcinogenic products. Nevertheless, significant reduction in mortality can be achieved by advances in early diagnosis and implementation of multidisciplinary treatment programs leading to improvement of survivorship and better quality of life. The present study was designed to evaluate the immunologic and biochemical markers in oral carcinogenesis using circulating immune complexes (CIC), copper, iron, and selenium concentrations as assessment endpoints. Study results indicated an increase in CIC and copper levels, and a decrease in iron and selenium concentrations in oral cancer patients compared to controls. The implications of these findings for public health are discussed.

Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial.

AIM: To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. METHODS: Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment.

Botox: the poison that heals.

The application of Botulinum toxin has become a useful and significant tool for oral and maxillofacial lesions. The art of using Botulinum toxin, a technical procedure, is influenced by aesthetic judgement and applications that extend beyond its use of reducing wrinkles to improve facial forms and shape. Novel uses for this unique substance will continue to permeate many medical and surgical specialties. Botulinum toxin delivered using more precise techniques may permit improved results without undesired consequences.

Wild cat bite--a narrow escape.

An unusual case is reported of a tiger bite and trauma to the maxillofacial region of a 45-year-old male patient. Wild animal assaults on the general population are on the increase in India and it is possible that further such cases will occur. The increased attacks could be a result of massive deforestation, resulting in disturbance to the ecosystem and tampering of the natural habitat of the royal cat.