Melastoma is a genus that belongs to the Melastomataceae family and consists of 50–70 species distributed around India, Southeast Asia, Australia and the Pacific Island. Numerous species of this plant show potential therapeutic purposes. This review summarizes the scientific findings on the ethnobotanical uses, phytochemistry and pharmacological activities of Melastoma sp. The leaves of Melastoma sp. was widely used by Asian as decoction for the remedy of gastrointestinal disorder apart from root, which was consumed as juice for skin diseases, fever and pain. Majority of the scientific studies focused on M. malabathricum showing high antimicrobial activity towards selected gram-negative and gram-positive bacteria from different parts of the plant. In vitro studies showed that Melastoma sp. possessed anti-coagulant, antioxidant, antiproliferative and immunomodulatory activities. Apart from in vitro, various in vivo studies have been conducted involving methanolic leaf extracts using Sprague Dawley rats for inhibition of anti-ulcer, anti-nociceptive, anti-inflammatory, anti-carcinogenic and anti-diabetic activities. Flavonoids, triterpenes, tannins, saponins and steroids are the main classes of secondary metabolites identified from Melastoma sp. Kaempferol derivatives exhibited significant main constituents from the flowers and leaves using various semi polar solvent extracts. Few phytosterols were also isolated from the leaves extract albeit the absence of alkaloids. This review shows that Melastoma sp. is an important genus of Melastomataceae family, however, the phytochemical and pharmacological findings of various species in this genus are still limited, indicating a great opportunity to explore new therapeutic activities with novel bioactive constituents.
Pharmacological

Introduction: Dental anxiety is a common problem faced by dental practitioners worldwide. Generally, the management of dental anxiety can be classified as pharmacological and non-pharmacological approaches, in multiple studies and reports available on this subject. Aims and objectives: This paper will provide a general overview of the pharmacological and nonpharmacological strategies in the management of dental anxiety, supported by dental literature. This would help dental practitioners understand the benefits and limitations of the different methods of treating their anxious patients. Methodology: This is a narrative review and a summary of the different approaches and methods available in the management of dental anxiety. Relevant articles were searched from the online databases of PubMed, ScienceDirect, and Google Scholar, and the keywords used to identify the papers were ‘Dental Anxiety’, ‘Pharmacological’, and ‘Non-pharmacological’. Conclusion Appropriate management of dental anxiety is crucial to ensure a successful dental procedure. The choice of the anxiety management must be based on the complete understanding of the particular patient, identifying the source of anxiety, and working hand-in-hand with the patient for better oral health care.
Dental Anxiety ; Pharmacological

OBJECTIVES: Recently, comparison of drug responses on gene expression has been a major approach to identifying the functional similarity of drugs. Previous studies have mostly focused on a single feature, the expression differences of individual genes. We provide a more robust and accurate method to compare the functional similarity of drugs by diversifying the features of comparison in gene expression and considering the sample dependent variations. METHODS: For differentially expressed gene measurement, we modified the conventional t-test to normalize variations in diverse experimental conditions of individual samples. To extract significant differentially co-expressed gene modules, we searched maximal cliques among the co-expressed gene network. Finally, we calculated a combined similarity score by averaging the two scaled scores from the above two measurements. RESULTS: This method shows significant performance improvement in comparison to other approaches in the test with Connectivity Map data. In the test to find the drugs based on their own expression profiles with leave-one-out cross validation, the proposed method showed an area under the curve (AUC) score of 0.99, which is much higher than scores obtained with previous methods, ranging from 0.71 to 0.93. In the drug networks, we could find well clustered drugs having the same target proteins and novel relations among drugs implying the possibility of drug repurposing. CONCLUSIONS: Inclusion of the features of a co-expressed module provides more implications to infer drug action. We propose that this method be used to find collaborative cellular mechanisms associated with drug action and to simply identify drugs having similar responses.
Biomarkers, Pharmacological ; Drug Repositioning ; Gene Expression Regulation ; Gene Expression* ; Gene Regulatory Networks ; Methods ; Transcriptome*

In order to prove safety and efficacy, herbal medicines must undergo the rigorous scientific researches such as pharmacokinetic and bioavailability, before they are put on the market in the foreign countries. Botanical Drug Products promulgated by the US FDA could guide industry sponsors to develop herbal drugs, which was also an important reference for investigating Chinese herbal medicines. This paper reviews and discusses novel approaches for how to assess systemic exposure and pharmacokinetic of Chinese herbal medicines, which were in line with FDA guidance. This mainly focus on identifying pharmacokinetic markers of botanical products, integral pharmacokinetic study of multiple components, Biopharmaceutics drug disposition classification system, and population pharmacokinetic-pharmacodynamic study in herb-drug interaction.
Animals ; Biomarkers, Pharmacological ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Herb-Drug Interactions ; Herbal Medicine ; legislation & jurisprudence ; Humans

The basic action mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitor is to lower the glucose burden by excreting the glucose filtered by the kidney into the urine. Although SGLT2 inhibitors are primarily indicated as glucose-lowering agents, they have a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. That might be why SGLT2 inhibition causes spill-over of sodium and glucose beyond the proximal tubule, triggering dynamic and reversible realignment of energy metabolism, renal filtration, and plasma volume. A better understanding of SGLT2 inhibition in the kidney and the entire body will lead to more benefits in people with and without diabetes.
Adiposity ; Diabetes Mellitus ; Energy Metabolism ; Filtration ; Glucose ; Homeostasis ; Kidney ; Molecular Mechanisms of Pharmacological Action ; Plasma Volume ; Sodium

Metabonomics is a new "-omics" science in post-gene time. Metabonomics can directly understand the physiological and biochemical situation by its "metabolome profile" as a whole, and therefore can provide various information that differs from other "-omics". Metabonomics has been applied in disease diagnosis, assessment of animal models, screening of new drugs, evaluation of drug safety, discovery of new bio-markers of toxicity, as well as research of traditional Chinese medicine.
Animals ; Biomarkers, Pharmacological ; metabolism ; Biomedical Research ; Diagnosis ; Drug Evaluation, Preclinical ; Humans ; Medicine, Chinese Traditional ; Metabolome ; Metabolomics ; Models, Animal ; Toxicity Tests

PURPOSE: Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response. MATERIALS AND METHODS: A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month. RESULTS: Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target. CONCLUSION: Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.
Adult ; Aged ; Biomarkers, Pharmacological/blood ; Calcium/blood ; Female ; Humans ; Hyperparathyroidism, Secondary/*drug therapy ; Male ; Middle Aged ; Naphthalenes/adverse effects/*therapeutic use ; Parathyroid Hormone/*blood ; *Renal Dialysis ; Treatment Outcome

Curcumin, which is extracted from the plant Curcuma longa, has been used in the therapeutic arsenal for clinical oncology. Curcumin has chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The expressions and activities of various proteins, such as inflammatory cytokines and enzymes, transcription factors, and gene-products linked with cell survivals and proliferation, can be modified by curcumin. Moreover, curcumin decreases the toxic effect of mitomycin C. Though curcumin has shown highly cytotoxic to some cancer cell lines, curcumin is insoluble and instable in water. The solubility of curcumin could be enhanced by utilizing the solubilizing properties of rubusoside. In addition, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors may improve the chemopreventive and chemotherapeutic effects. The focus of this short review is to describe how curcumin participates in antitumor processes in breast cancer cells.
Breast ; Breast Neoplasms ; Cell Line ; Curcuma ; Curcumin ; Cytokines ; Diterpenes, Kaurane ; Glucosides ; Imidazoles ; Medical Oncology ; Mitomycin ; Molecular Mechanisms of Pharmacological Action ; Niacin ; Plants ; Proteins ; Solubility ; Transcription Factors ; Water

Recently traditional Chinese medicine (TCM)-induced liver injury has been an unresolved critical issue which impacts TCM clinical safety. The premise and key step to reduce or avoid drug-induced liver injury (DILI) is to identify the drug source of liver injury in early stage. Then the timely withdrawal of drug and treatment can be done. However, the current diagnosis of DILI is primarily governed by exclusive method relying on administering history supplied by patients and experience judgment from doctors, which lacks objective and reliable diagnostic indices. It is obvious that diagnosis of TCM-induced liver injury is especially difficult due to the complicated composition of TCM medication, as well the frequent combination of Chinese and Western drugs in clinic. In this paper, we proposed construction of research pattern and method for objective identification of TCM-related DILI based on translational toxicology, which utilizes clinical specimen to find specific biomarkers and characteristic blood-entering constituents, as well the clinical biochemistry and liver biopsy. With integration of diagnosis marker database, bibliographic database, medical record database and clinical specimen database, an integrative diagnosis database for TCM-related DILI can be established, which would make a transformation of clinical identification pattern for TCM-induced liver injury from subjective and exclusive to objective and index-supporting mode. This would be helpful to improve rational uses of TCM and promote sustainable development of TCM industry.
Animals ; Biomarkers, Pharmacological ; metabolism ; Biopsy ; methods ; Chemical and Drug Induced Liver Injury ; diagnosis ; metabolism ; pathology ; Early Diagnosis ; Humans ; Liver ; drug effects ; pathology ; Medicine, Chinese Traditional ; adverse effects ; Rats

PURPOSE: Identification of subgroups of patients who differ in their response to treatment could help to establish which of the best available chemotherapeutic options are best, based on biological activity. In metastatic colorectal cancer (CRC), novel molecular-targeted agents that act on pathways that regulate cell growth, the cell cycle, apoptosis, angiogenesis, and invasion are being developed. Here, we employed an in vitro chemosensitivity assay to evaluate the biological efficacy of conventional monotherapies and combination chemotherapy with targeted drugs. METHODS: The chemosensitivities of 12 CRC cell lines to the established regimens FOLFOX (5-fluorouracil [5-FU] + leucovorin + oxaliplatin) and FOLFIRI (5-FU + leucovorin + irinotecan) and to therapy with these regimens in combination with the biologically targeted drugs bevacizumab or cetuximab were comparatively evaluated for their effects on apoptotic and autophagic cell death processes, angiogenesis, and invasion. RESULTS: Each of the chemotherapeutic regimens promoted apoptotic cell death and invasion. All drug regimens caused significantly greater apoptotic cell death with activation of caspase-3 in SW480 cells compared to other cells, effects that were associated with a remarkable reduction in matrix metalloproteinase-9 activity. The FOLFOX regimen more effectively promoted apoptotic cell death, angiogenesis, and invasion than the FOLFIRI regimen. Combination therapy with FOLFOX/FOLFIRI regimen and bevacizumab produced a moderate angiogenesis-blocking effect in most cell lines. CONCLUSION: The results validate our in vitro chemosensitivity assay, and suggest that it may be applied to help determine adequate regimens in individual CRC patients based on the biological characteristics of their tumors.
Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; Apoptosis ; Autophagy ; Bevacizumab ; Biomarkers, Pharmacological ; Caspase 3 ; Cell Cycle ; Cell Death ; Cell Line ; Cetuximab ; Colorectal Neoplasms ; Drug Therapy, Combination ; Fluorouracil ; Humans ; Leucovorin ; Matrix Metalloproteinase 9 ; Organoplatinum Compounds ; Population Characteristics