Ricinus communis L. (R. communis), commonly known as castor oil plant, is used as a traditional natural remedy or folkloric herb for the control and treatment of a wide range of diseases around the globe. Various studies have revealed the presence of diverse phytochemicals such as alkaloids, flavonoids, terpenes, saponins, phenolic compounds such as kaempferol, gallic acid, ricin, rutin, lupeol, ricinoleic acid, pinene, thujone and gentisic acid. These phytochemicals have been responsible for pharmacological and therapeutic effects, including anticancer, antimicrobial, insecticidal, antioxidant, anti-diabetic, antinociceptive, anti-inflammatory, bone regenerative, analgesic, and anticonvulsant activity. R. communis harbours phytochemicals which have been shown to target peroxisome proliferator activated receptor (PPAR), nuclear factor NF- κ -B, cytochrome p450, P38 mitogen-activated protein kinases kinase (p38 MAPK), tumor protein P53, B-cell lymphoma-extra-large (Bcl-xL) and vascular endothelial growth factor receptor-2 (VEGFR-2). Considering its wide variety of phytochemicals, its pharmacological activity and the subsequent clinical trials, R. communis could be a good candidate for discovering novel complementary drugs. Further experimental and advanced clinical studies are required to explore the pharmaceutical, beneficial therapeutic and safety prospects of R. communis with its phytochemicals as a herbal and complementary medicine for combating various diseases and disorders.

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Breast cancer is a frightful disease and serious concern in women around the world causing significant health care burden in both developed and developing countries. Extensive research work has shown that breast cancer provides strong resistance to chemical agents, UV radiation, and hormonal treatments. It is generally accepted that cell genetics is not the only main reason for breast cancer and genetic risk factors, for example, mutations in BRCA1 and BRCA2 genes constitute 5%-10% of all breast cancer rates. Other related factors include age, gender, race, ethnicity, weight, reproductive factors, exo- and endogenous hormonal exposures, oral contraceptives use, ultraviolet radiation, diet, and night work (circadian disruption). Many studies have revealed that dietary isoflavones regulate breast cancer occurrence, recurrence and prognosis. Dietary isoflavones have long been part of Asian population diet and there is a significant increase as compared to dietary isoflavones intake among other populations. Dietary isoflavones are natural phytoestrogens having both estrogenic and anti-estrogenic potentials on breast cancer cells in culture, animal models and in experimental trials. This literature survey provides a comprehensive overview on the tumor preventive and tumor promoting potentials of dietary isoflavones on breast cancer. In addition, this paper provides a literature review of dietary isoflavones and their effects on up-regulation and down-regulation of different signaling pathways, genes and proteins. Finally, future perspectives of dietary isoflavones and breast cancer researchers are also critically discussed, which will provide a deeper insight regarding the inner molecular mechanisms of action.

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Objective: To study the effects of some common additives on the antimicrobial activities of alcohol-based hand sanitizers. Methods: The antibacterial activities of varying aqueous concentrations of ethanol and isopropyl alcohol were tested by the agar well diffusion method. The influences of different concentrations of glycerin was similarly tested. Finally, isopropyl alcohol and benzalkonium chloride were combined in different ratios within the safe use concentrations of each, and the effects of these combinations were compared with values obtained for the two agents used alone. Statistical methods, such as student t test and one-way ANOVA were used when appropriate to evaluate the differences in activity. Results: The activities of the alcohols showed marked concentration dependence, and both showed peak activity at 85%–95% concentration range. Over the concentration range of 60%–100%, isopropyl alcohol inhibited more bacterial and fungal organisms than ethanol, though the inhibition zone diameters it produced were not statistically different from those of ethanol for organisms which were sensitive to both of them. Addition of glycerin reduced the antimicrobial activities of the isopropyl alcohol, as shown by reduction in the inhibition zone diameters produced in vitro, which may be due to reduced drug diffusion with increase in viscosity. Addition of benzalkonium to isopropyl alcohol systems improved the activity of the alcohol, but the overall activity of the combination was not superior to that seen in the use of benzalkonium alone. Conclusion: Alcohol-based hand sanitizers should not be used outside the concentration range of 85%–95% and isopropyl alcohol inhibits more bacterial and fungal organisms than ethanol for most concentrations. Inclusion of benzalkonium improves the antimicrobial spectrum and activity of isopropyl alcohol, and the combination may justifiably be used to achieve both immediate and long lasting effect. Glycerin may adversely affect the antimicrobial activities of isopropyl alcohol-based hand sanitizers and should be used with caution.

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Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus (CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results: The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-1 cell line. In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further, andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R, phosphorylated eukaryotic initiation factor 2α , retinoic acid inducible gene-I and interferon regulatory factor 3/7, thereby increasing IFN- α secretion. CHIKV-induced nuclear factor κ light chain enhancer of activated B cells and tumor necrosis factor- α was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.

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Objective: To explore the therapeutic effect and mechanism of myricetin on disseminated intravascular coagulation (DIC). Methods: The DIC model was established by injection of 60 mg/kg LPS in KM mice, and the treatment groups were injected myricetin with different concentrations (25 or 50 mg/kg) 30 min before the model was established. Both coagulation indicators and organ function were tested, including PT, APTT, fibrinogen, AST, ALT, BUN and tissue section. In vitro, the inflammatory model of RAW 264.7 macrophage cells were established by 10 μg/mL LPS. The treatment group was treated with 50 μmol/mL myricetin for 30 min before LPS, and the expression of TNF-α and p-NF-κB was detected, further to explore the therapeutic mechanism. Results: LPS-induced DIC led to a reduction of fibrinogen and a rise of PT, APTT, AST, ALT, BUN levels, but the treatment of myricetin significantly inhibited these abnormalities. Histopathology analysis also revealed that myricetin remarkably protected the liver and renal damage. In vitro, the expression of TNF-α and p-NF-κB induced by LPS was repressed by myricetin. Conclusions: This study provides new insights into the protective effects of myricetin in LPS-induced DIC by anticoagulant and anti-inflammatory via suppressing the activation of p-NF-κB which decreased TNF-α level.

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Objective: To analyze the largest outbreak of dengue in Argentina in the municipality of Tigre during 2016, through detailed spatial analyses of the occurrence of cases in relation to demographic factors and vector control actions. Methods: Detailed and georreferenced data on dengue cases with laboratory results (NS1 or IgM) were analyzed. The occurrences of imported and autochthonous cases by census tract were modeled using demographic variables (population by age class, proportion of foreigners, proportion with university grade, proportion of males), dwelling variables (number of homes, proportion of dwellings with latrine, number of dwellings, proportion of houses, proportion of flats, proportion of slums) and census tract area as explanatory variables. The probability of occurrence of autochthonous and imported cases was modeled separately. The spatio-temporal occurrence of cases was studied in relation to focal and perifocal control actions (involving education campaigns, removal of Aedes aegypti breeding sites and exhaustive insecticide spraying) to assess the efficiency in stopping autochthonous cases spreading. Results: All autochthonous cases occurred in the urban environment with no sylvan cases. The majority of the imported cases registered came from Paraguay and Northeastern Argentina. The age structure of imported and autochthonous cases did not differ from the age structure of the municipality, while that of the negative cases did. When studied spatially, the occurrence of imported cases by census tract was mildly associated with a higher proportion of foreign population and more people at active age, while occurrence of autochthonous cases was not significantly associated with any of the studied variables. For census tracts with laboratory confirmed results, the models showed higher probability of autochthonous cases related to higher population density and population age structure. The clustering of autochthonous cases was generally mild, with prevailing isolated cases and a weak spread inside the municipality. The biggest outbreak focus was associated with a delay in the focal vector control. Conclusions: Results confirmed the virus pressure coming from neighboring countries and related to population movement by workers. All autochthonous cases occurred in the urban environment with no sylvan cases. The susceptibility of residents to dengue may be similar among age classes and the laboratory tests were performed more frequently in the younger. Autochthonous cases incidence was low and spatio-temporal clustering of cases weak, suggesting that control measures were effective when no delay occurred in their application.

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Objective: To investigate whether the extract from the nacreous layer of pearl oysters (nacre extract) improves impairments in memory caused by scopolamine administration in rodents. Methods: Nacre extract was prepared from the inner shell layer of pearl oyster. Effects of nacre extract on scopolamine-induced memory impairment were estimated using novel object recognition test, Y-maze test, and Barnes maze test. Effect of nacre extract on mRNA expressions which are genes associated with memory in the hippocampus was investigated using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: Administration of nacre extract led to the protection against scopolamine-induced impairments in object recognition, short-term memory, and spatial memory. Treatment with nacre extract reversed the mRNA expression of brain-derived neurotrophic factor (BDNF) and Homer protein homolog 1 (Homer-la) in the hippocampus, which decreased with the treatment of scopolamine. Conclusions: These results suggest that nacre extract has attenuating effects on memory impairments induced by scopolamine through the increase in mRNA expression of BDNF and Homer-1a.

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Objective: To highlight the relationship between miR-503 and wound healing of diabetic foot ulcer (DFU). Methods: Microarray analysis was used to detect the dysregulated miRNAs between the DFU tissues and normal tissues. The expression of miR-503 in tissues and serum of patients with DFU was detected by qRT-PCR technique. Then, CCK-8 assay was applied to determine the cell proliferation. TUNEL assay was used for assessing the apoptosis of cells after treatment with miR-503. Possible correlation between miR-503 and fbillin1 (FBN1) was predicted according to data accessed on RNA22 website online, and was detected for confirmation by luciferase reporter assay. Results: Microarray analysis showed that miR- 503 was significantly decreased in the DFU tissues compared with normal tissues. While marked increase in the expression of miR-503 in tissues and serum of patients with DFU was confirmed by qRT-PCR technique. Then, CCK-8 assay indicated that transfection of miR- 503 mimic obviously accelerated the cell proliferation. However, TUNEL assays suggested that miR-503 mimic inhibited the apoptosis of cells to improve the survival of fibroblasts. Besides, miR-503 AMO played a role in fibroblasts of DFU tissues exactly countering to miR-503 mimic treatment. It was predicted that MiR-503 is a complementary to the FBN1 by RNA22. Besides, SiRNA-FBN1 promoted the proliferation, but brought down the apoptosis of fibroblasts. Conclusions: MiR-503 regulates the function of fibroblasts and wound healing of patients with DFU by targeting FBN1 directly which provids a novel and critical target for diagnosis and treatment of DFU.

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Objective: To evaluate the evolution of the pathogen Mayaro virus, causing Mayaro fever (a mosquito-borne disease) and to perform selective pressure analysis and homology modelling. Methods: Nine different datasets were built, one for each protein (from protein C to non-structural protein 4) and the last one for the complete genome. Selective pressure and homology modelling analyses were applied. Results: Two main clades (A and B) were pointed in the maximum likelihood tree. The clade A included five Brazilian sequences sampled from 1955 to 2015. The Brazilian sequence sampled in 2014 significantly clustered with the Haitian sequence sampled in 2015. The clade B included the remaining 27 sequences sampled in the Central and Southern America from 1957 to 2013. Selective pressure analysis revealed several sites under episodic diversifying selection in envelope surface glycoprotein E1, non-structural protein 1 and non- structural protein 3 with a posterior probability P≤0.01. Homology modelling showed different sites modified by selective pressure and some protein-protein interaction sites at high interaction propensity. Conclusion: Maximum likelihood analysis confirmed the Mayaro virus previous circulation in Haiti and the successful spread to the Caribbean and USA. Selective pressure analysis revealed a strong presence of negatively selected sites, suggesting a probable purging of deleterious polymorphisms in functional genes. Homology model showed the position 31, under selective pressure, located in the edge of the ADP-ribose binding site predicting to possess a high potential of protein-protein interaction and suggesting the possible chance for a protective vaccine, thus preventing Mayaro virus urbanization as with Chikungunya virus.

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Objective: To evaluate the hepatic and renal protective potential of coriander seeds and leaves using animal feed model. Methods: Coriander seeds- and leaves-based sauces were administrated to normal (Study I) and carbon tetrachloride (2 mL/kg B.W.)-induced hepatotoxic rabbits (Study II). Hepatic and renal biomarkers like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, superoxide dismutase and catalase were measured. Results: Coriander leaves-based sauce exerted more decline (P<0.05) in serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase levels in the study II as 18.32%, 19.91% and 21.24%, respectively. While, hepatic superoxide dismutase and catalase levels were raised significantly (P<0.05) in both studies. Renal parameters also depicted positive impact by the provision of developed sauces. Conclusions: Coriander seeds and leaves based sauces are effective in alleviating the hepato/renal toxicity. The hepatoprotective effect of coriander leaves is more pronounced as compared to coriander seeds.

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Objective: To investigate the role of ClC-3 chloride channel in the proliferation of breast cancer cell line Mcf-7 treated with curcumin and its specific mechanism. Methods: MTT assay was used to detect the effect of chloride channel blocker (DIDS) and curcumin on Mcf-7 and human normal cell viability. Patch-clamp technique was used to determine the current density before and after drug treatment. Apoptosis assay by flow cytometry was performed for further examination of cell apoptosis. Results: Curcumin had toxicity on Mcf-7 and HUVEC cells and DIDS reduced the survival rate of Mcf-7 cells by inhibiting proliferation. Curcumin could activate the chloride ion current on MCF-7 cell membrane, which would be inhibited by DIDS. Finally, curcumin in low concentration combined with DIDS could significantly promote the MCF-7 cells apoptosis. Conclusions: Our results suggest that ClC-3 protein is involved in the regulation of curcumin induced proliferation inhibiting in breast cancer cells through inducing cell apoptosis. ClC-3 may be a potential target of tumor therapy.

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Objective: To investigate the effects of steroidal alkaloids and sarcovagine D isolated from Sarcococca hookeriana var. digyna on cell-proliferation and secretion of inflammatory cytokines in TNF-α-induced human RA-FLS MH7A in vitro, and against complete Freund’s adjuvant (CFA)-induced arthritis rats in vivo. Methods: CCK-8 assay was utilized to evaluate the anti-proliferation activity in vitro. In in-vivo study, rats were randomly divided into control group, model group (CFA), steroidal alkaloids (STA) groups (5.0, 2.5 and 1.25 g/kg BW), and sarcovagine D (SD) groups (50, 100 and 200 mg/kg BW), 10 rats for each group. To evaluate the anti-inflammation effect, the histology, biochemical parameters and expression of inflammatory cytokines were detected. Results: Steroidal alkaloids and sarcovagine D showed strong anti-proliferative activity during MH7A cell culture proliferation and downregulated NO levels, and inflammatory cytokines (IL-1ß, IL-6 and PGE₂) in vitro. The rats treated with CFA induced ankle inflammation and lymphocyte infiltration, upregulated IL-1ß, TNF-α, IL-6, PGE₂, MDA and NO levels, and downregulated IL-10 and SOD. On the contrary, steroidal alkaloids ameliorated all the changes induced by CFA in rats, suggesting the anti-inflammatory effect of steroidal alkaloids and sarcovagine D. Conclusions: The results suggest that Sarcococca hookeriana var. digyna has anti-inflammatory effect. Steroidal alkaloids and sarcovagine D has the potential to cure RA.

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Objective: To detect the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island. Methods: Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBL2 in serum was detected by ELISA. Results: We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group (P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P=0.028). Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier (P=0.014, 0R=2.550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0.05). Conclusions: The variation of rs1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.

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Objective: To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells. Methods: Regenerated tissue extracts after liver injury were used to induce SK-HEP1 cells after enrichment, their effects on the proliferation, differentiation, migration and invasion of SK-HEP1 cells were observed through in vitro cell culture, MTT, flow cytometry and transwell assays. Results: In response to the action of regenerated tissue extracts after liver injury, SK-HEP1 cells were blocked in G_0/G₁ phase, their growth rate was distinctly reduced. The number of SK-HEP1^{- fj} colonies decreased. The migration ability of SK-HEP1 cells showed a decreased trend on day 7 and day 11 after induction. SK-HEPl’s invasion ability clearly decreased on days 7 and 11 after induction, especially on day 7. Conclusions: To a certain extent, regenerated tissue extracts after liver injury can inhibit the proliferation, differentiation, migration and invasion of hepatoma cells, showing an important potential of being a differentiating agent for the treatment of liver cancer.

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