Anticancer potential of Ferula assa-foetida and its constituents,a powerful plant for cancer therapy

Cancer is one of the main challenges of the health system around the world. This disease is increasing in developing countries and imposes heavy costs on patients and governments. On the other hand, despite various drugs, the death rate among cancer patients is still high and the current treatments have many harmful effects. In the traditional medicine of different countries, there are many medicinal plants that can be effective in the treatment of cancer. Ferula plants are traditionally used as spices and food or for medicinal purposes. Ferula assa-foetida is one of the famous plants of this genus, which has been used for the treatment of various diseases since ancient times. Among the main compounds of this plant, we can mention monoterpenes, sulfide compounds and polyphenols, which can show different therapeutic effects. This article has been compiled with the aim of collecting evidence and articles related to the anti-cancer effects of extracts, derived compounds, essential oils and nanoparticles containing Ferula assa-foetida. This review article was prepared by searching the terms Ferula assa-foetida and cancer, and relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Fortunately, the results of this review showed that relatively comprehensive studies have been conducted in this field and shown that Ferula assa-foetida can be very promising in the treatment of cancer.     

Burden of Giardia duodenalis Infection and Its Adverse Effects on Growth of Schoolchildren in Rural Malaysia

Background

Giardia duodenalis infection and malnutrition are still considered as public health problems in many developing countries especially among children in rural communities. This study was carried out among Aboriginal (Orang Asli) primary schoolchildren in rural peninsular Malaysia to investigate the burden and the effects of Giardia infection on growth (weight and height) of the children.

Methods/Findings

Weight and height of 374 children aged 7–12 years were assessed before and after treatment of Giardia infection. The children were screened for Giardia parasite using trichrome staining technique. Demographic and socioeconomic data were collected via face-to-face interviews using a pre-tested questionnaire. Overall, 22.2% (83/374) of the children were found to be infected with Giardia. Nutritional status of children was assessed and the results showed that the mean weight and height were 23.9 kg (95% CI = 23.3, 24.5) and 126.6 cm (95% CI = 125.6, 127.5), respectively. Overall, the prevalence of severe underweight, stunting and wasting were 28.3%, 23.8% and 21.0%, respectively. Multiple linear regression analyses showed sex, Giardia infection and household monthly income as the significant determinants of weight while sex and level of mother''s education were the significant determinants of height. Weight and height were assessed at 3 and 6 months after treatment of Giardia infection. It was found that Giardia infection has a significant association with the weight of children but not with height.

Conclusions/Significance

This study reveals high prevalence of Giardia infection and malnutrition among Aboriginal children in rural Malaysia and clearly highlights an urgent need to identify integrated measures to control these health problems in the rural communities. Essentially, proper attention should be given to the control of Giardia infection in Aboriginal communities as this constitutes one of the strategies to improve the nutritional status of Aboriginal children.     

The Suitability of P. falciparum Merozoite Surface Proteins 1 and 2 as Genetic Markers for In Vivo Drug Trials in Yemen

Background

The accuracy of the conclusions from in vivo efficacy anti-malarial drug trials depends on distinguishing between recrudescences and re-infections which is accomplished by genotyping genes coding P. falciparum merozoite surface 1 (MSP1) and MSP2. However, the reliability of the PCR analysis depends on the genetic markers’ allelic diversity and variant frequency. In this study the genetic diversity of the genes coding for MSP1 and MSP2 was obtained for P. falciparum parasites circulating in Yemen.

Methods

Blood samples were collected from 511 patients with fever and screened for malaria parasites using Giemsa-stained blood films. A total 74 samples were infected with P. falciparum, and the genetic diversity was assessed by nested PCR targeting Pfmsp1 (Block2) and Pfmsp2 (block 3).

Results

Overall, 58%, 28% and 54% of the isolates harboured parasites of the Pfmsp1 K1, MAD20 and RO33 allelic families, and 55% and 89% harboured those of the Pfmsp2 FC27 and 3D7 allelic families, respectively. For both genetic makers, the multiplicity of the infection (MOI) was significantly higher in the isolates from the foothills/coastland areas as compared to those from the highland (P<0.05). Pfmsp2 had higher number of distinct allelic variants than Pfmsp1 (20 vs 11). The expected heterozygosity (HE) for Pfmsp1 and Pfmsp2 were 0.82 and 0.94, respectively. Nonetheless, a bias in the frequency distribution of the Pfmsp1 allelic variants was noted from all areas, and of those of Pfmsp2 in the samples collected from the highland areas.

Conclusions

Significant differences in the complexity and allelic diversity of Pfmsp1 and Pfmsp2 genes between areas probably reflect differences in the intensity of malaria transmission. The biased distribution of allelic variants suggests that in Yemen Pfmsp1 should not be used for PCR correction of in vivo clinical trials outcomes, and that caution should be exercised when employing Pfmsp2.     

Mutations in BICD2, which Encodes a Golgin and Important Motor Adaptor,Cause Congenital Autosomal-Dominant Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Here, we identified pathogenic variants in bicaudal D homolog 2 (Drosophila) (BICD2) in three families afflicted with autosomal-dominant SMA. Affected individuals displayed congenital slowly progressive muscle weakness mainly of the lower limbs and congenital contractures. In a large Dutch family, linkage analysis identified a 9q22.3 locus in which exome sequencing uncovered c.320C>T (p.Ser107Leu) in BICD2. Sequencing of 23 additional families affected by dominant SMA led to the identification of pathogenic variants in one family from Canada (c.2108C>T [p.Thr703Met]) and one from the Netherlands (c.563A>C [p.Asn188Thr]). BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport. Transient transfection of HeLa cells with all three mutant BICD2 cDNAs caused massive Golgi fragmentation. This observation was even more prominent in primary fibroblasts from an individual harboring c.2108C>T (p.Thr703Met) (affecting the C-terminal coiled-coil domain) and slightly less evident in individuals with c.563A>C (p.Asn188Thr) (affecting the N-terminal coiled-coil domain). Furthermore, BICD2 levels were reduced in affected individuals and trapped within the fragmented Golgi. Previous studies have shown that Drosophila mutant BicD causes reduced larvae locomotion by impaired clathrin-mediated synaptic endocytosis in neuromuscular junctions. These data emphasize the relevance of BICD2 in synaptic-vesicle recycling and support the conclusion that BICD2 mutations cause congenital slowly progressive dominant SMA.     

Environmental Suitability and Distribution of the Caucasian Rock Agama, Paralaudakia caucasia （Sauria： Agamidae） in Western and Central Asia

Predictive potential distribution modeling is crucial in outlining habitat usage and establishing conservation management priorities. In this paper we provide detailed data on the distribution of the Caucasian rock agama Para- laudakia caucasia, and use species distribution models （MAXENT） to evaluate environmental suitability and potential distribution at a broad spatial scale. Locality data on the distribution of P. caucasia have been gathered over nearly its entire range by various authors from field surveys. The distribution model ofP caucasia showed good performance （AUC = 0.887）, and predicted high suitability in regions mainly located in Tajikistan, north Pakistan, Afghanistan, southeast Turkmenistan, northeast Iran along the Elburz mountains, Transcaueasus （Azerbajan, Armenia, Georgia）, northeastern Turkey and northward along the Caspian Sea coast in Daghestan, Russia. The identification of suitable areas for this species will help to assess conservation status of the species, and to set up management programs.     

Comparison of Th1 and Th2 responses in non-healing and healing patients with cutaneous leishmaniasis

Background:

Cutaneous leishmaniasis is an endemic disease in many regions of Iran, including the city of Mashhad. In recent years, some cases have not responded to Glucantime, the usual treatment for this disease. The cellular immune response caused by T-helper type 1 (Th1) cells has an important role in protection against leishmaniasis, and activation of the T-helper type 2 (Th2) response causes progression of the disease. By analyzing these responses we hope to find a more effective treatment than that currently in use for leishmaniasis patients.

Methods:

The cellular immune responses in 60 cases of non-healing and healing cutaneous leishmaniasis, and individuals in a control group, were analyzed by measuring cytokines released by peripheral blood mononuclear cells (PBMCs) when stimulated with Leishmania major antigens by Enzyme Linked Immuno Sorbent Assay (ELISA).

Results:

Subjects from the healing group secreted more interleukin-12 (IL-12) and interferon gamma (IFN-γ) (p<0.05) and less interleukins -4, -5, -10 (IL-4, IL-5, and IL-10) (p<0.005) and -18 (IL-18) (p=0.003) than the non-healing group.

Conclusions:

The results demonstrate that secretion of cytokines that activate Th2 response including IL-4, IL-5 and IL-10 in non-healing subjects was higher than healing subjects and secretion of cytokines that activate Th1 response including IL-12 and IFN-γ in healing subjects was higher relative to the non-healing subjects. In this study it has been shown that the level of IL-18 progresses disease in non-healing patients when the level of IL-12 gets decreased. Key Words: Cytokines, Cutaneous leishmaniasis, Glucantime     

Diversity and Antimicrobial Activity of Actinomycetes Isolated from Lut Desert: The Extremely Arid Climatic Zones of Iran

Lut desert is situated in one of the extremely arid climatic zones of Iran and is one of the hottest deserts in our plant with the extreme fluctuation of temperature over a day. The main objective of this study is to characterize the diversity of the culturable actinomycetes and preliminary evaluation of their extracts as antimicrobial components on drug resistant pathogens. Twenty-four soil samples were collected, successively diluted and inoculated into the different culture media to support the growth of most culturable bacteria including actinomycetes. Phenotypic and molecular methods were used for accurate identification of recovered isolates particularly actinomycetes at the genus and species levels. The isolates were also evaluated for their inhibitory activities against drug resistant Acinetobacter baumannii, Enterococcus faecium, Klebsiella pneumoniae and Staphylococcus aureus. A total of 56 isolates recovered from the samples. Based on phenotypic tests, 41 isolates were identified as actinomycetes, amongst them 8 isolates were active against drug resistant pathogens. Our study revealed Lut desert, as one of the hottest deserts in the world, is the habitat to diverse taxa of bacteria particularly actinomycetes which have potential novel antimicrobial components.

     

In vivo and in vitro evidence for the involvement of Nrf2-antioxidant response element signaling pathway in the inflammation and oxidative stress induced by particulate matter (PM10): the effective role of gallic acid

Environmental pollution is one of the risk factors for respiratory diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is the major mechanisms contributing to cellular defense against oxidative damage. Gallic acid (GA) is regarded as potent anti-inflammatory and antioxidant agents. The aim was to evaluate the role of Nrf2 pathway in particulate matter (PM₁₀) exposure on lung and epithelial cells with an emphasis on the role of GA. In in vivo part, the rats were divided as control, GA (30?mg/kg), particulate matter (PM) (0.5, 2.5, and 5?mg/kg), and PM?+?GA. In in vitro study, the cells were divided as control, PM₁₀ (100, 250, and 500?µg/ml), GA (50 µmol/L) and PM₁₀+GA. Inflammation, oxidative stress and Nrf2-pathway factors were assessed. PM₁₀ groups showed a considerable increase in the epithelial permeability and inflammatory parameters. We also found a significant decrease in the expression of Nrf2 and its up-stream regulators genes. Accordingly, the biosynthesis of glutathione (GSH) and other antioxidant activities significantly decreased. Gallic acid was identified to restore the antioxidant status to the normal levels. Our findings approved that Nrf2 is involved in PM₁₀-induced oxidative damages and showed that Nrf2 activation by natural agents could ameliorate respiratory injuries induced by PM₁₀.     

Herbal medicine as an auspicious therapeutic approach for the eradication of Helicobacter pylori infection: A concise review

Helicobacter pylori (H. pylori) causes gastric mucosa inflammation and gastric cancer mostly via several virulence factors. Induction of proinflammatory pathways plays a crucial role in chronic inflammation, gastric carcinoma, and H. pylori pathogenesis. Herbal medicines (HMs) are nontoxic, inexpensive, and mostly anti-inflammatory reminding meticulous emphasis on the elimination of H. pylori and gastric cancer. Several HM has exerted paramount anti-H. pylori traits. In addition, they exert anti-inflammatory effects through several cellular circuits such as inhibition of 5′-adenosine monophosphate-activated protein kinase, nuclear factor-κB, and activator protein-1 pathway activation leading to the inhibition of proinflammatory cytokines (interleukin 1α [IL-1α], IL-1β, IL-6, IL-8, IL-12, interferon γ, and tumor necrosis factor-α) expression. Furthermore, they inhibit nitrous oxide release and COX-2 and iNOS activity. The apoptosis induction in Th1 and Th17-polarized lymphocytes and M2-macrophagic polarization and STAT6 activation has also been exhibited. Thus, their exact consumable amount has not been revealed, and clinical trials are needed to achieve optimal concentration and their pharmacokinetics. In the aspect of bioavailability, solubility, absorption, and metabolism of herbal compounds, nanocarriers such as poly lactideco-glycolide-based loading and related formulations are helpful. Noticeably, combined therapies accompanied by probiotics can also be examined for better clearance of gastric mucosa. In addition, downregulation of inflammatory microRNAs (miRNAs) by HMs and upregulation of those anti-inflammatory miRNAs is proposed to protect the gastric mucosa. Thus there is anticipation that in near future HM-based formulations and proper delivery systems are possibly applicable against gastric cancer or other ailments because of H. pylori.