Comparative Evaluation of the Potential Antitumor of Helleborus purpurascens in Skin and Breast Cancer

In the field of oncology, the plant kingdom has an inexhaustible supply of bioactive compounds. Phytochemical compounds isolated from Helleborus species have been found to be useful in various chronic diseases. This has brought Helleborus to the attention of medical researchers. H. purpurascens is a plant characteristic of the Carpathian area, known since ancient times for its beneficial effects. The aim of the study was to evaluate the flavonoids composition of a hydroalcoholic extract of H. purpurascens, as well as to assess its antioxidant activity and antitumor potential at the level of two healthy cell lines and four tumor cell lines. In addition, the expression of the genes involved in the apoptotic process (Bcl-2, Bad, and Bax) were evaluated. The results indicated that the extract has a high concentration of flavonoids, such as epicatechin, quercetin, and kaempferol. The extract has an increased antioxidant activity, very similar to that of the standard, ascorbic acid and cytotoxic effects predominantly in the breast cancer cell line, being free of cytotoxic effects in healthy cell lines. Underlying the cytotoxic effect is the induction of the process of apoptosis, which in the present study was highlighted by decreasing the expression of anti-apoptotic genes (Bcl-2) and increasing the expression of pro-apoptotic genes (Bad and Bax). In conclusion, the hydroalcoholic extract of H. purpurascens can be considered an important source for future medical applications in cancer therapy.

Melatonin, tunneling nanotubes and anastasis: Cheating cell death

When healthy neurons are exposed to toxins or physiological insults such as ischemia, apoptosis is often initiated. Once underway, this mechanistically-well described process was thought to routinely run its course with the disintegration of the cell and phagocytosis of the debris. Within the last decade, the consistency of this process has been questioned. It is now known that some damaged cells can recover, i.e., they avoid death; this restoration process is referred to as anastasis. The reestablishment of a healthy cell phenotype is highly energy-requiring, so optimally functioning mitochondria are obviously beneficial during the regenerative process. Some healthy mitochondria that end up in regenerating cells are transferred there by adjacent healthier cells through tunneling nanotubes. Tunneling nanotubes generally form under stressful conditions when these micron-size tubules link adjacent cells. These tubules transfer soluble factors and organelles, including mitochondria, between the connected cells. When damaged cells receive high APT-producing mitochondria via this means, they support the ability of the cells to recover. Two recent comprehensive publications show that melatonin aids the transfer of mitochondria through nanotubes that connect neurons thereby likely assisting the recovery of the damaged recipient cell. Thus, melatonin not only protects normal neurons from damage by neutralizing the agents that initiate apoptosis, e.g., free radicals, etc., but also reverses this process once it is underway.

In Vitro Phytochemical Screening, Cytotoxicity Studies of Curcuma longa Extracts with Isolation and Characterisation of Their Isolated Compounds

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (1H Proton and 13C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC50value of 11.27 μg/mL,and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC50 value 16.79 μg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC50 value of 93.28 μg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin.

Synthesis of New 1-Aryl-2-(3,5-dimethylpyrazol-1-yl)ethanone Oxime Ether Derivatives and Investigation of Their Cytotoxic Effects

In this study, 12 new 1-aryl-2-(3,5-dimethylpyrazol-1-yl)ethanone oxime ether derivatives were designed and synthesized to investigate their cytotoxic effects. The in vitro cytotoxic activities of the compounds were evaluated against cervix, colon, breast, glioma, neuroblastoma, and lung cancer cell lines, as well as a healthy cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide (MTT) assays with 5-fluorouracil (5-FU) as the reference compound. Compound 5f (IC50 = 5.13 µM) was found to be more effective than 5-FU (IC50 = 8.34 µM) in the C6 cancer cell line, and it had no cytotoxic effect on the L929 healthy cell line. Flow cytometry was used to investigate the mechanism of action of compound 5f on the cell cycle of the C6 cell line. The analysis showed that cell death was significantly due to apoptosis. These results indicate that compound 5f induces cell cycle arrest, and may be effective in treating glioma.

Cardiac aorta-derived extracellular matrix scaffold enhances critical mediators of angiogenesis in isoproterenol-induced myocardial infarction mice

An incapability to improve lost cardiac muscle caused by acute ischemic injury remains the most important deficiency of current treatments to prevent heart failure. We investigated whether cardiomyocytes culturing on cardiac aorta-derived extracellular matrix scaffold has advantageous effects on cardiomyocytes survival and angiogenesis biomarkers’ expression. Ten male NMRI mice were randomly divided into two groups: (1) control (healthy mice) and (2) myocardial infarction (MI)-induced model group (Isoproterenol/subcutaneously injection/single dose of 85 mg/kg). Two days after isoproterenol injection, all animals were sacrificed to isolate cardiomyocytes from myocardium tissues. The fresh thoracic aorta was obtained from male NMRI mice and decellularized using 4% sodium deoxycholate and 2000 kU DNase-I treatments. Control and MI-derived cardiomyocytes were seeded on decellularized cardiac aorta (DCA) considered three-dimensional (3D) cultures. To compare, the isolated cardiomyocytes from control and MI groups were also cultured as a two-dimensional (2D) culture system for 14 days. The cell viability was examined by MTT assay. The expression levels of Hif-1α and VEGF genes and VEGFR1 protein were tested by real-time PCR and western blotting, respectively. Moreover, the amount of VEGF protein was evaluated in the conditional media of the 2D and 3D systems. The oxidative stress was assessed via MDA assay. Hif-1α and VEGF genes were downregulated in MI groups compared to controls. However, the resulting data showed that decellularized cardiac aorta matrices positively affect the expression of Hif-1α and VEGF genes. The expression level of VEGFR1 protein was significantly (p ≤ 0.01) upregulated in both MI and healthy cell groups cultured on decellularized cardiac aorta matrices as a 3D system compared to the MI cell group cultured in the 2D systems. Furthermore, MDA concentration significantly decreased in 3D-cultured cells (MI and healthy cell groups) rather than the 2D-cultured MI group (p ≤ 0.015). The findings suggest that cardiac aorta-derived extracellular scaffold by preserving VEGF, improving the cell viability, and stimulating angiogenesis via upregulating Hif-1α, VEGF, and VEGFR1 in cardiomyocytes could be considered as a potential approach along with another therapeutic method to reduce the complications of myocardial infarction and control the progressive pathological conditions related to MI.

Polyamines: Functions, Metabolism, and Role in Human Disease Management

Putrescine, spermine, and spermidine are the important polyamines (PAs), found in all living organisms. PAs are formed by the decarboxylation of amino acids, and they facilitate cell growth and development via different cellular responses. PAs are the integrated part of the cellular and genetic metabolism and help in transcription, translation, signaling, and post-translational modifications. At the cellular level, PA concentration may influence the condition of various diseases in the body. For instance, a high PA level is detrimental to patients suffering from aging, cognitive impairment, and cancer. The levels of PAs decline with age in humans, which is associated with different health disorders. On the other hand, PAs reduce the risk of many cardiovascular diseases and increase longevity, when taken in an optimum quantity. Therefore, a controlled diet is an easy way to maintain the level of PAs in the body. Based on the nutritional intake of PAs, healthy cell functioning can be maintained. Moreover, several diseases can also be controlled to a higher extend via maintaining the metabolism of PAs. The present review discusses the types, important functions, and metabolism of PAs in humans. It also highlights the nutritional role of PAs in the prevention of various diseases.

Levofloxacin Might be Safe to use for OSCC Patients

PurposeSince oral squamous cell carcinoma (OSCC) patients are exhausted against the powerful chemotherapies and radiotherapies after surgeries, therefore most of the studies still look for less toxic but effective alternatives with new ideas such as antibiotic combinations.MethodsThe antiproliferative and apoptotic outcomes of levofloxacin with cisplatin combination as well as their single usage were examined with WST-1, Caspase-3/BCA and Annexin-V methods on SCC-15 cells and on a healthy cell line (MRC-5).Results24h treatment of 50 mM single levofloxacin, 50 mM single cisplatin and 50 mM levofloxacin-cisplatin combination resulted in cell viability rates of SCC-15 cells as 90%, 67% and 80.8% respectively. Caspase-3 enzyme activity was enhanced 0.92-fold for single levofloxacin, 13.05-fold for single cisplatin and 9.73-fold for the combination of levofloxacin-cisplatin, the total apoptotic activity of single levofloxacin, single cisplatin and levofloxacin-cisplatin combination were observed as 4.88%, 21.14% and 16.21% respectively on SCC-15. Also MRC-5 were showed the lower toxicity than cancer cells via apoptosis.ConclusionLevofloxacin-cisplatin combination results have also ended up apoptotic results with less toxicity for cells than single cisplatin treatment. Therefore, our apoptotic findings suggest that the different dosage combinations with levofloxacin and cisplatin are necessary to understand the interaction for the treatment of tongue squamous cell carcinoma.

Ex-Vivo Detection of Breast Cancer with a Bio-Impedance Sensor

Bioimpedance is the opposition to flow of an applied electrical current through biological tissues1. Our research group designed and fabricated bipolar micro-sensors on the tip of a silicone probe, capable of measuring biological tissue impedance. It is known that the bioimpedance of cultured cancer cells differs substantially from that of healthy cell lines. We hypothesised that the bioimpedance of cancer in surgically excised human tissue would be significantly different to surrounding healthy tissue. To test this hypothesis, we designed a study to evaluate the bioimpedance of healthy and diseased breast tissue in surgically excised breast specimens. This manuscript reports the outcome of this study.

KARNINI YONIVYAPAD W.S.R TO CERVICAL EROSION – A CASE STUDY

Karnini Yonivyapad is described with its own pathogenesis and treatment in classical text. It can be compared with cervical erosion due to its clinical appearance. Among all Yonivyapad, only this Yonivyapad is related with cell pathology. In present circumstances when cervical intraepithelial neoplasia, cervical cancer are the burning issues in front of whole world, it is necessary to understand physiology and pathology of cervix in benign stages so that an appropriate prevention or treatment can be done at this stage. An ideal and complete treatment of pathological erosion should be that which destroy the ectopic columnar epithelium and make healthy cell environment so that regression of erosion will take place properly. Virechana karma is the radical purification that eliminates waste products, toxins and aggravated doshas from the body. As aggravated Doshas are the primary cause of disease, this method is the most direct for curative purposes. In present study, patient with Karnini yonivyapada is treated with combination of Shodhan, shaman and local therapy. Trivrit Lehya has been selected for Virechana karma because in all the herbs easy and safe among purgative is Trivrit. Apamarga (Achyranthes aspera L.) kshar Tail used for Yoni pichu and Triphala Guggul is selected for Shaman chikitsa, which is seen to be very much effective.