Objective: To investigate the anti-inflammatory properties of methanolic extract of Clausena excavata in lipopolysaccharide (LPS)-activated macrophages (J774A.1) and the effect on skin wound in a rat model through determining cytokine levels and gene expressions. Methods: The effects of methanolic extract of Clausena excavata on in vitro viability and TNF-α, IL-6, IL-10, and nitric oxide release by LPS-activated J774A.1 cells were determined. In addition, relative expressions of BAX, BCL-2 and COX-2 genes were examined in healed wounds of rats. Results: The methanolic extract of Clausena excavata was not toxic to J774A.1 cells at the highest dose of 400 μg/mL. It decreased levels of TNF-α and IL-6, while increasing IL-10 level in LPS- activated J774A.1 cells and in the healed wounds of rats. The methanolic extract of Clausena excavata also inhibited nitric oxide production in LPS-activated J774A.1 cells. The BAX and COX-2 genes were downregulated while the BCL-2 gene was upregulated in the healed wound of rats. Conclusions: The methanolic extract of Clausena excavata promotes wound healing via its anti-inflammatory and anti-apoptotic activities.

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Objective: To determine the diversity of sand flies in different biotopes of mountainous and plain areas of Bam County as the most infected focus of anthroponotic cutaneous leishmaniasis in southeast Iran, and synanthropic index of Phlebotomus sergenti Parrot, and Phlebotomus papatasi Scopoli as the main vectors of cutaneous leishmaniasis in Iran. Methods: Sand flies were captured once a month using sticky traps in domestic, peri-domestic, agricultural, and sylvatic biotopes in the plain and mountainous areas. Alpha diversity indices, including richness, evenness, Shannon-Wiener; beta diversity indices (Jaccard’s and Sorensen’s similarity indices) and synanthropic index were calculated. Results: A total of 2 664 specimens of 9 sand fly species were collected from mountainous (47%) and plain (53%) areas. Species richness, species evenness, and Shannon-Wiener indices were obtained as 9, 0.637, and 1.399, respectively in the mountainous area. Phlebotomus sergenti and Phlebotomus papatasi were constant species with the synanthropic index of -18.463 and -29.412, respectively. In addition, species richness, species evenness, and Shannon-Wiener indices were 4, 0.690, and 0.956, respectively in the plain area. Phlebotomus sergenti and Phlebotomus papatasi were dominant species with the synanthropic index of +9.695 and +36.207, respectively. Similarity indices were low among different biotopes of plain and mountainous areas. Conclusions: A basic knowledge about the diversity of sand flies in various biotopes is essential to design sound control programs. Biodiversity and synanthropic indices of sand flies are different in plain and mountainous areas due to the difference in biotic and abiotic factors between the two areas.

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Objective: To investigate whether piperlongumine can sensitize prostate cancer cells to tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) and trigger apoptosis in prostate cells. Methods: Human prostate cancer cell lines PC3, LNCaP, and VCaP were cultured with piperlongumine and TRAIL. Then, cell proliferation, migration, caspase activation, apoptotic protein expressions, and death receptor expressions were measured. Results: Piperlongumine inhibited cell proliferation at low doses (<10 μM) alone and in combination with TRAIL (25 ng/mL), induced apoptosis, and suppressed cyclooxygenase activation. Additionally, piperlongumine induced expression of death receptors which potentiated TRAIL-induced apoptosis in cancer cells but did not affect decoy receptors. Piperlongumine also downregulated tumor cell-survival pathways, inhibited colony formation and migration of cancer cells alone or in combination with TRAIL. The combination of piperlongumine with TRAIL was found to be synergistic. Conclusions: Our findings indicate that piperlongumine can sensitize cancer cells to TRAIL through the upregulation of death receptors and can trigger apoptosis with the downregulation of anti- apoptotic proteins.

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Objective: To explore the inhibitory effect of water extract from pear pomace on abdominal fat accumulation and its underlying mechanism in high fat diet-fed animals. Methods: Three groups of male C57BL/6J mice were fed with a 60% kcal fat diet for 8 weeks. Pear pomace water extract (200 or 400 mg/kg body weight) was administered once daily via oral gavage. To confirm the possibility of the water extract of pear pomace acting as an activator of adenosine 5’-monophosphate- activated protein kinase (AMPK), differentiation of 3T3-L1 preadipocytes was induced in the presence of the water extract of pear pomace with or without compound C. Body weight, food efficacy ratio, insulin resistance, and adipogenic protein expression were measured. Moreover, in the 3T3-L1 cells, lipid content and lipogenesis-related proteins were measured using Oil Red O staining and Western blotting analysis. Results: Body weight gain and total abdominal fat weight were reduced in mice treated with pear pomace water extract. Pear pomace water extract reduced fasting blood glucose and insulin, thereby reducing the homeostatic model assessment of insulin resistance. It also resulted in dose-dependent decreases in triglyceride, total cholesterol, and low-density lipoprotein- cholesterol. The protein expression of p-AMPK increased, while the expression of AMPK-downstream proteins including PPAR-γ, C/ EBPa, SREBP-1c, ACC, and FAS decreased in the adipose tissue of mice treated with pear pomace water extract. Furthermore, the inhibition of AMPK by compound C blocked pear pomace water extract-induced reduction of lipid content and the expression of lipogenesis-related genes. Conclusions: Pear pomace water extract prevents fat accumulation both in vivo and in vitro by activating AMPK.

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The unprecedented resurgence and geographical expansion of arboviral infections such as dengue, Chikungunya, yellow fever, and Zika have a significant impact on human health and pose a serious threat to public health globally in recent years. Zika virus is a Flavivirus and is transmitted to humans through an infected mosquito bite. The Zika virus has been identified in many countries in Africa, Asia, and Pacific islands and sporadic human cases have been reported since 1947. The non-specific clinical symptoms of Zika fever are often misdiagnosed with other arboviral infections, especially dengue and chikungunya. Till now, there is no vaccine or specific antiviral treatment for Zika infection. The recent emergence of Zika is alarming and highlights the need for arboviral research to develop an effective treatment. Here in this review, we discussed the epidemiology of Zika, which has re-emerged in the recent decade and caused international concern.

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Objective: To investigate the cytotoxic effects and the potential mechanisms of crebanine N-oxide in SGC-7901 gastric adenocarcinoma cells. Methods: The cytotoxicity of crebanine N-oxide was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and cellular morphology was observed under a microscope. Cell apoptosis was determined by flow cytometry using propidium iodide staining. The expression levels of apoptotic-related proteins, cleaved caspase-3, cytochrome C, p53 and Bax, and autophagy- related proteins p62, beclin1 and LC3 were detected by Western blotting assays. Results: Crebanine N-oxide treatment significantly inhibited the proliferation of SGC-7901 cells in a dose-dependent and time- dependent manner via induction of G₂-phase cell cycle arrest, apoptosis, and autophagy in SGC-7901 cells. Conclusions: Crebanine N-oxide could inhibit the growth of gastric cancer cells by promoting apoptosis and autophagy and could be used as a potential agent for treating gastric cancer.

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