Investigation of the cellular and molecular effects of dehydrozingerone formulation on various days of diabetic wound repair.

Cases of diabetes are significantly increasing year by year, attracting the attention of medical professionals and researchers to focus on diabetes and its underlying complications. One among such are diabetic wounds which are difficult to heal, creating severe implications in the day-to-day chores of not only patients, but also family members. Dehydrozingerone (DHZ) is known to possess various effects like anti-inflammatory, anti-microbial, antioxidant, and wound-healing properties. The effect of DHZ on different phases of diabetic wound healing remains untested. Hence, this study was proposed to find out the effect of oral and topical formulation of DHZ on day 5, 10 and 15 of diabetic wound healing. Excisional wounds were created on the dorsal side of animals using punch biopsy to mimic human diabetic wounds. Topical DHZ gel (100 mg in 1 gm of gel) was prepared using 1% Carbopol 934 and was applied twice a day. The treated groups had increased percentage of wound closure; western blotting suggested that DHZ significantly increased ERK and JNK levels and decreased TNF and MMP 2 and 9 levels. From histopathological studies, it was observed that angiogenesis, collagen formation, granulation tissue formation, and fibroblast proliferation were improved on days 5, 10, and 15 of diabetic wound healing. These findings indicate that DHZ (both systemic and topical) are effective during the early phases of wound healing which gets impaired in diabetic wounds. Dehydrozingerone accelerated diabetic wound healing by regulating the various hallmarks of wound healing process.

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A needs to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions.

The Cervical Abrasion Index of Treatment Needs (CAITN) Procedure for Population Groups and Individuals.

Because of their complex epidemiology and etiology, cervical abrasions usually manifest with concealing symptoms. The buccolingual dimension of the sore is considered the most important metric to rank the damage and evaluate its long-term prognosis. In this piece, we will break this down and offer the Cervical Abrasion Index of Treatment Needs (CAITN), a simple grouping structure based on the clinical presentation of the sore that may be used to establish a basic, useful, treatment-based order. CAITN is the practical approach to routine screening and recording cervical abrasion lesions. The index provides epidemiologists, public health professionals, and practitioners with a practical means of assessing the treatment needs (TN) of cervical abrasion.

Assessment of Cervical Abrasion, Dentin Hypersensitivity, and Its Treatment Needs Using the Cervical Abrasion Index of Treatment Needs Probe.

Objective This study was intended to compare the mean buccolingual measurement of abraded teeth with/without sensitivity. The hypothesis was that the suggested treatment approaches would be in agreement with that of the treatment needs (TN) elicited using the Cervical Abrasion Index of Treatment Needs (CAITN) probe and aid in the development of a prospective CAITN index for clinical/community studies of effective therapeutic measures. Materials and methods  A cross-sectional study was carried out on 30 individuals with a mean age of 48.4±12.54 years, comprising 840 teeth with/without cervical abrasion. The buccolingual measurement of each tooth was recorded using the CAITN probe. The response to air-blast was assessed by a short blast of one-second duration at a distance of 1 cm for each tooth. An endodontist was also asked to indicate the treatment methods used by him for the treatment of abrasions. His opinions regarding the TN were later compared with the data collected by an investigator. Results The mean buccolingual measurements of all the teeth were compared with the dentinal sensitivity using the independent t-test and were statistically highly significant. Furthermore, one-way analysis of variance disclosed that there was a statistically highly significant difference found for all the TN (p<0.01) such as none, preventive, basic, and advanced restorative TN followed by Tukey honestly significant difference post hoc tests for multiple pair-wise comparisons. The running receiver operator characteristic curve discloses the best cut-off value of the buccolingual measurement to predict the various categories of TN of each tooth. As the area under the curve is more close to 1 (noticed in the majority of the teeth in the sample), the model predicts the TN more precisely based on the buccolingual measurements. Conclusion The present study enables a correct diagnosis of cervical abrasions and determines the various TN with the most appropriate restorative material. These baseline data help to design clinical studies that test relevant treatment and diagnostic strategies.

Emphasizing roles of BDNF promoters and inducers in Alzheimer's disease for improving impaired cognition and memory.

Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons' development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer's disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus' BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.

Diabetic wound healing approaches: an update.

Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.

Dehydrozingerone promotes healing of diabetic foot ulcers: a molecular insight.

INTRODUCTION: One of the most common problems of diabetes are diabetic foot ulcers (DFUs). According to National Institute for Health, initial management of DFUs can decrease the complication of limb amputations and can improve the patient's quality of life. DFU treatment can be optimized with the help of multidisciplinary approach. Based on many studies, control of glucose levels in blood, antioxidant activity, reduction in cytokine levels, re-epithelialization, collagen formation, migration of fibroblasts are major phases involved in managing DFU. Dehydrozingerone (DHZ), has been known for its anti-inflammatory, antioxidant and wound healing properties. METHODOLOGY: Three months high-fat diet and low dose of streptozotocin-induced type-II diabetic foot ulcer model was used to evaluate the effectiveness of dehydrozingerone. DHZ was given orally to rats for 15 days post wounding. TNF-α, IL-1ß and antioxidant parameters like lipid peroxidation, glutathione reductase were estimated. Immunoblotting was done to investigate the effect of DHZ on the expression of ERK, JNK, HSP-27, P38, SIRT-1, NFκB, SMA, VEGF and MMP-9 in skin tissue. Histopathology was performed for analyzing DHZ effect on migration of fibroblasts, formation of epithelium, granulation tissue formation, angiogenesis and collagen formation. RESULTS: DHZ decreased the levels of malondialdehyde, TNF-α, IL-1ß and increased glutathione levels in wound tissue. Western blotting results suggested that DHZ activated ERK1/2/JNK/p38 signaling, increased expression of HSP-27, SIRT-1, VEGF, SMA thus facilitating the migration and proliferation of fibroblasts, angiogenesis and decreased inflammation. Masson Trichrome & histopathology showed an increase in collagen, epithelial and granulation tissue formation. CONCLUSION: DHZ significantly accelerates the healing of diabetic foot ulcers in high fat diet fed plus low dose streptozotocin induced type-II diabetic Wistar rats.

Nanoparticle-mediated active and passive drug targeting in oral squamous cell carcinoma: current trends and advances.

Oral squamous cell carcinoma (OSCC) is an invasive and highly malignant cancer with significant morbidity and mortality. Existing treatments including surgery, chemotherapy and radiation have poor overall survival rates and prognosis. The intended therapeutic effects of chemotherapy are limited by drug resistance, systemic toxicity and adverse effects. This review explores advances in OSCC treatment, with a focus on lipid-based platforms (solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrids, cubosomes), polymeric nanoparticles, self-assembling nucleoside nanoparticles, dendrimers, magnetic nanovectors, graphene oxide nanostructures, stimuli-responsive nanoparticles, gene therapy, folic acid receptor targeting, gastrin-releasing peptide receptor targeting, fibroblast activation protein targeting, urokinase-type plasminogen activator receptor targeting, biotin receptor targeting and transferrin receptor targeting. This review also highlights oncolytic viruses as OSCC therapy candidates.

Cervical Abrasion, Sexual Dimorphism, and Anthropometric Tooth Dimension.

Introduction: The aim of this study was to analyze the anatomic crowns of the maxillary and mandibular dentition concerning the mesiodistal, buccolingual measurements which will be used to establish normative data as a part of comprehensive study being carried out to determine the depth of the cervical abrasion (CA) of the individuals by predicting the CA Index of Treatment Needs (CAITN) score. Materials and Methods: A newly developed instrument termed as CAITN probe was used to measure CA of the tooth more quantitatively. The mesiodistal and buccolingual width of all the 14 maxillary and mandibular teeth from the right second permanent molar to the left second permanent molar of the study sample was measured. The ratio between buccolingual and mesiodistal measurements of each tooth of the maxillary and mandibular arch of the study sample (n=100) was also determined. Statistical analysis was performed using the SPSS 26.0 software. Results: Descriptive statistics were calculated for each group independently. The statistical significance of the difference in mean in mesiodistal and buccolingual diameters between males and females was calculated using the t-test for independent samples with p < 0.05. The ratio was highest in the left second premolar (1.752) and least in the right central incisor (0.980) of the maxillary arch. Similarly, the ratio was highest in the left central incisor (1.723) and least in the left second molar (0.910) of the mandibular arch. Conclusion: The present study was conducted as an initial step in the process of development of the novel tool or index enabling the dentists to organize the health-care needs of their patients by facilitating standardized identification of CA with objective measurements used for epidemiological or community purpose.

Association Between Cervical Abrasion, Oral Hygiene Practices and Buccolingual Dimension of Tooth Surfaces: A Cross-Sectional Study.

Background: Cervical abrasion is a multifactorial process due to the use of abrasive dentifrices along with improper brushing patterns. An extensive lesion may cause loss of structural integrity of tooth and esthetically unacceptable. The purpose of the study was to assess the prevalence of cervical abrasion with age, gender, and oral hygiene practices among workers in a spinning mill, Kerala. The study also aimed to identify the buccolingual measurements of each abraded tooth using the Community Abrasion Index of Treatment Needs (CAITN) probe. Materials and Methods: A cross-sectional study where 366 subjects (257 males and 109 females) above 20 years of age were selected using a random sampling technique. Data was collected from the assessment form comprising demographic data and oral hygiene practices of the subjects. Clinical examination for abrasion and buccolingual measurements of abraded tooth recorded using CAITN probe. The statistical analysis was done using SPSS 26.0. for calculating descriptive statistics, Chi-square test, and binary logistic regression. Results: The overall prevalence of abrasion was 37.2% and 97.7% of subjects with abrasion had sensitive teeth and were statistically significant. Age, gender (males) and combined horizontal and vertical method of brushing technique were strongly associated with the cervical lesion (P < 0.001). Binary logistic regression analysis showed that age group, gender, combined horizontal and vertical method of brushing, and presence of sensitive tooth was associated with the abrasion. Conclusion: It is concluded that the severity of the abrasion is an age-related phenomenon associated with combined horizontal and vertical strokes of brushing and is common among the male population. Dentinal hypersensitivity is also more prevalent with cervical abrasion. The novel CAITN probe can be used as an effective tool to assess the cervical abrasion and its treatment needs.

The Design, Development, and Calibration of Cervical Abrasion Index of Treatment Needs Probe for Measurement of Cervical Abrasion.

Context: Although a common dental problem, there are no simple instruments or reliable methods to measure cervical abrasion. Aim: To study the design, development, calibration, efficacy, and compliance of usage of a novel Cervical Abrasion Index of Treatment Need (CAITN) probe to measure cervical abrasion. Settings and Design: The ex-vivo study was conducted as a part of comprehensive study for the development of standardized CAITN probe and index with a standard methodology for recording the abrasion. Materials and Methods: The compliance and usage of the probe were assessed by a standardized set of questionnaires to the interns followed by an ex-vivo study in 100 subjects. Gold standard comparisons with Vernier caliper, inter-examiner, and intra-examiner reliability were analyzed using SPSS. Results: Data from the questionnaire indicate that 100% of examiners had no difficulty in handling the instrument or measuring and reading the values. Comparison between the CAITN probe and the gold standard was statistically significant indicating a correlation for cervical abrasion measurement between the two methods (p < 0.001). The mean difference between the two measurements using the CAITN probe and gold standard method was calculated with paired t-test and was insignificant (p > 0.05). High statistical significant correlation was also found for intra-examiner and inter-examiner reliability measurement of CAITN probe (p < 0.001). Conclusion: The design and structure of the CAITN probe are standardized with a fair gold standard comparison and that the novel probe can be used as an effective tool to measure the depth of cervical abrasion and its treatment needs.

Sirtuins as therapeutic targets for improving delayed wound healing in diabetes.

Sirtuins are a vast family of histone deacetylases, which are NAD+ dependent enzymes, consisting of seven members, namely SIRT 1, SIRT 6 and SIRT 7 located within the nucleus, SIRT 2 in the cytoplasm and SIRT 3, SIRT 4 and SIRT 5 in the mitochondria. They have vital roles in regulating various biological functions such as age-related metabolic disorders, inflammation, stress response, cardiovascular and neuronal functions. Delayed wound healing is one of the complication of diabetes, which can lead to lower limb amputation if not treated timely. SIRT 1, 3 and 6 are potent targets for diabetic wound healing. SIRT 1 deficiency reduces recruitment of fibroblasts, macrophages, mast cells, neutrophils to wound site and delays wound healing; negatively expressing MMP-9. The SIRT 1 mediated signalling pathway in diabetic wound healing is the SIRT 1-FOXO-c-Myc pathway. On the contrary, SIRT 3 deficiency impairs proliferation and migration of fibroblasts and SIRT 6 deficiency impairs wound closure rate and interrupts the vascular remodelling. This review focuses on the role of sirtuins in improving delayed wound healing in diabetes and its natural modulators with their specific functions towards healing diabetic wounds.

Notch signaling: A possible therapeutic target and its role in diabetic foot ulcers.

BACKGROUND & AIM: Diabetic foot ulcers are major cause of lower limb amputations in the diabetic population. The major factors that play a role in causing the delay of the process of healing in diabetic foot ulcers broadly are decreased angiogenesis, reduced proliferation and migration of keratinocytes/fibroblasts. The typical wound healing process has four phases which are overlapping with each other thus making the healing even more complex. Hence it is essential to identify a therapeutic target that involves the regulation of the cellular factors involved in healing and helps to increase angiogenesis and can regulate all four phases accordingly. METHOD: Literature review involved a search of the databases namely, PubMed, Cochrane, EMBASE, and Web of Science database. Articles were identified and retrieved that specifically dealt with Notch as a target in healing of wounds and its mechanism of action on various cells and phases of healing. RESULTS: Notch is a cell surface receptor which interacts with transmembrane ligands of the nearby cells and is involved in cell proliferation, differentiation, cell fate and death. It is also involved in cell-to-cell communication, cell signaling, and various phases of development. There exist four known notch genes and five ligands which interact with notch proteins. Hyperglycemia plays a role in the activation of the notch receptor thus causing the release of inflammatory mediators via macrophages. As notch can regulate macrophage-mediated inflammation it can serve as a therapeutic target for diabetic foot ulcers. CONCLUSION: This review focuses on the effect of notch on various cell mediators and phases of diabetic wound healing and deals with how notch activation or inhibition can serve as a potential therapeutic target for healing diabetic foot ulcers.

Comparative Evaluation of Salivary Sialic Acid Levels Among Beedi Rollers and Tobacco Users in Mangalore, South India.

INTRODUCTION: According to World Health Organization, the global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. Tobacco use is a leading cause of cancer and of death from cancer. Beedis are the most popular smoking form of tobacco in India. Thirty-four percent of the tobacco produced in India is used for making beedis. The beedi sector is agroforestry-based and the second largest industry in India with approximately 4.4 million full-time beedi workers in India. Toxic constituents present in tobacco are released into the ambient air during the processing of beedis. METHODS: A descriptive cross-sectional study was conducted to assess and compare salivary sialic acid levels among beedi rollers, tobacco smokers, smokeless tobacco users and individuals with no tobacco exposure. The study sample comprised of 140 individuals who were 30 to 60 years old, who attended dental screening and treatment camps in rural and urban areas in Mangalore, conducted by the Department of Public Health Dentistry, Yenepoya Dental College and patients who visited the Department of Oral Medicine and Radiology of Yenepoya Dental College. Saliva was collected by passive drool method into a sterile container. Biochemical analysis of salivary sialic acid was done using the acidic ninhydrin method. Continuous variables are expressed in terms of mean and standard deviation. Categorical variables are expressed in terms of frequencies and percentages. To compare salivary sialic acid levels between the groups ANOVA was used. The Chi-square test was used to compare categorical variables between the groups. RESULTS: A total of 140 participants, 35 beedi rollers, 35 smokers, 35 smokeless tobacco users and 35 individuals with no tobacco exposure participated in the study. Among the 140 participants, 90 participants were males and 50 participants were females. There was a statistically significant difference in the mean salivary sialic acid level between the different groups (p<0.001) with smokeless tobacco users having the highest (10.60 mg/dL) mean salivary sialic acid level. It was found that the mean salivary sialic acid level reduced as the age progressed, even though there was no statistically significant difference. There was a statistically significant difference in the mean salivary sialic acid level between the different groups (p=0.010) with participants with 11 to 20 years of exposure to tobacco having the highest (8.67 mg/dL) mean salivary sialic acid level and participants with no tobacco exposure having least (3.06 mg/dL) mean salivary sialic acid level. CONCLUSION: The salivary sialic acid level was more in beedi rollers than individuals with no tobacco exposure, even though the difference was not statistically significant. The results showed elevated levels of salivary sialic acid in smokeless tobacco users followed by tobacco smokers. This may be an indication that smokeless tobacco use has harmful effects similar to or more than tobacco smoking since salivary sialic acid levels in smokeless tobacco users were higher than those in smokers.

Role of Statins in New-onset Diabetes Mellitus: The Underlying Cause, Mechanisms Involved, and Strategies to Combat.

Statins have transformed the treatment of cardiovascular diseases through primary and secondary prevention of events. Despite the success of statin's management of cardiovascular conditions, certain clinical trials, reviews, and meta-analysis point out that statins have the propensity to induce diabetes. The risk further increases with intensive statin therapy or in patients with diabetes. A proper mechanism for the induction of the diabetic condition has not yet been determined. The involvement of statin with beta cells in insulin secretion and peripheral cells in insulin resistance has been widely studied and established. The present review provides an update on the recent understanding of statin-induced diabetes. This covers the origin of statins, their development, possible mechanisms that explain the adverse effects in glucose homeostasis, and probable targets to remedy the condition.

In silico Study to Evaluate the Antiviral Activity of Novel Structures against 3C-like Protease of Novel Coronavirus (COVID-19) and SARS-CoV.

BACKGROUND: Globally, over 4.3 million laboratory confirmed cases of COVID-19 have been reported from over 105 countries. No FDA approved antiviral is available for the treatment of this infection. Zhavoronkov et al., with their generative chemistry pipeline, have generated structures that can be potential novel drug-like inhibitors for COVID-19, provided they are validated. 3C-like protease (3CLP) is a homodimeric cysteine protease that is present in coronaviruses. Interestingly, 3CLP is 96.1% structurally similar between SARS-CoV and SARS-CoV-2. OBJECTIVE: To evaluate interaction of generated structures with 3CLP of SARS-CoV (RCSB PDB ID: 4MDS). METHODS: Crystal structure of human SARS-CoV with a non-covalent inhibitor with resolution: 1.598 Å was obtained and molecular docking was performed to evaluate the interaction with generated structures. The MM-GBSA and IFD-SP were performed to narrow down to the structures with better binding energy and IFD score. The ADME analysis was performed on top 5 hits and further MD simulation was employed for top 2 hits. RESULTS: In XP docking, IFD-SP and molecular dynamic simulation studies, the top 2 hits 32 and 61 showed interaction with key amino acid residue GLU166. Structure 61, also showed interaction with HIS164. These interactions of generated structure 32 and 61, with GLU166 and HIS164, indicate the binding of the selected drug within the close proximity of 3CLP. In the MD simulation, the protein- ligand complex of 4MDS and structure 61 was found to be more stable for 10ns. CONCLUSION: These identified structures can be further assessed for their antiviral activity to combat SARS-CoV and COVID-19.

Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats.

BACKGROUND: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition. METHODS: Sesamol-PLGA (SM-PLGA) nanosuspension was developed  using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections. RESULTS: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed. CONCLUSION: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.

Botrops derived hemocoagulase formulation a probable agent for diabetic wound healing.

Botroclot is a marketed preparation containing hemocoagulase, which is an enzyme having coagulant activity, isolated from the snake Botrops atrox. This formulation is used in dental surgeries and other minor surgical wounds. However, the formulation remains untested in diabetic wounds. Hence, we proposed a study for the topical application of Botroclot in high-fat diet (HFD) + Streptozotocin (STZ) induced diabetic rats. HFD was fed initially to rats which facilitates the development of insulin resistance. Thereafter, an injection of STZ (40 mg/kg, i.p.) was given. This resulted in the development of diabetes with elevated fasting glucose and impaired glucose tolerance. After stabilization of blood glucose values, wounds were created by punch biopsy on the dorsal side of the palm of the rat to mimic the diabetic wounds frequently seen in the case of humans. Later, the application of Botroclot on these wounds was carried out for 15 days. Topical application of hemocoagulase improved the wound closure and there was a gradual decrease in inflammatory markers and a substantial increase in collagen deposition occurred. Histopathological findings indicated the same, with an increase in granulation tissue suggesting that the topical application moderately improves the wound healing in diabetic rats. We conclude that Botroclot can have a mild to moderate effect in improving collagen deposition and thus wound contraction, improving wound closure in diabetic wounds in rats. This study also establishes the basis for exploration of agents from venom-based sources in diabetic wound healing.

An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review.

Sesame (Sesamum indicum L.) seeds have been authenticated for its medicinal value in both Chinese and Indian systems of medicine. Its numerous potential nutritional benefits are attributed to its main bioactive constituents, sesamol. As a result of those studies, several molecular mechanisms are emerging describing the pleiotropic biological effects of sesamol. This review summarized the most interesting in vitro and in vivo studies on the biological effects of sesamol. The present work summarises data available from Pubmed and Scopus database. Several molecular mechanisms have been elucidated describing the pleiotropic biological effects of sesamol. Its major therapeutic effects have been elicited in managing oxidative and inflammatory conditions, metabolic syndrome and mood disorders. Further, compelling evidence reflected the ability of sesamol in inhibiting proliferation of the inflammatory cell, prevention of invasion and angiogenesis via affecting multiple molecular targets and downstream mechanisms. Sesamol is a safe, non-toxic chemical that mediates anti-inflammatory effects by down-regulating the transcription of inflammatory markers such as cytokines, redox status, protein kinases, and enzymes that promote inflammation. In addition, sesamol also induces apoptosis in cancer cells via mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the present review, several pharmacological effects of sesamol are summarised namely, antioxidant, anti-cancer, neuroprotective, cardioprotective, anti-inflammatory, hypolipidemic, radioprotective, anti-aging, anti-ulcer, anti-dementia, anti-depressant, antiplatelet, anticonvulsant, anti-anxiolytic, wound healing, cosmetic (skin whitening), anti-microbial, matrix metalloproteinase (MMPs) inhibition, hepatoprotective activity and other biological effects. Here we have summarized the proposed mechanism behind these pharmacological effects.

Evaluation of Salivary Parameters and Oral Health Status Among Asthmatic and Nonasthmatic Adult Patients Visiting a Tertiary Care Hospital.

INTRODUCTION: Asthma is a chronic inflammatory disorder of the airways characterized by attacks of bronchoconstriction causing shortness of breath, coughing, and rapid breathing. Patients undergoing inhalation therapy are subjected to a higher risk of dental caries due to the reduced saliva secretion, decreased pH value, increased number of cariogenic bacteria caused by inappropriate oral hygiene, and the use of inhaling medicaments with dry powder. METHODS: The descriptive study was carried out among 200 patients aged (18-45 years) visiting Yenepoya Hospital, Mangalore during the period from May 2018 to October 2018 to evaluate salivary parameters and oral health status in asthmatic and nonasthmatic patients. Data were collected using WHO criteria (2013) and samples of unstimulated saliva were collected for evaluation of salivary flow rate, pH, buffering capacity, and calcium. Statistical analysis was done using SPSS version 21.0 software with the level of significance set at p < 0.05.  Results: A decreased mean score of salivary flow rate, pH, and buffering capacity were found in asthmatic patients compared to nonasthmatic patients (p < 0.001). A higher mean decayed, missing, and filled teeth (DMFT) score and an increased dental erosion score were found in asthmatics compared to nonasthmatics (p < 0.05). Asthmatics had higher gingival bleeding score than nonasthmatics. CONCLUSION:  In order to prevent disease progression in the hard dental tissue and oral cavity of asthmatic patients, it is necessary to apply adequate preventive measures and motivate their continuous application in this caries-risk population.