CRISPR Cas9 mediated knockout of sex determination pathway genes in Aedes aegypti.

The vector role of Aedes aegypti for viral diseases including dengue and dengue hemorrhagic fever makes it imperative for its proper control. Despite various adopted control strategies, genetic control measures have been recently focused against this vector. CRISPR Cas9 system is a recent and most efficient gene editing tool to target the sex determination pathway genes in Ae. aegypti. In the present study, CRISPR Cas9 system was used to knockout Ae. aegypti doublesex (Aaedsx) and Ae. aegypti sexlethal (AaeSxl) genes in Ae. aegypti embryos. The injection mixes with Cas9 protein (333 ng ul-1) and gRNAs (each at 100 ng ul-1) were injected into eggs. Injected eggs were allowed to hatch at 26 ± 1°C, 60 ± 10% RH. The survival and mortality rate was recorded in knockout Aaedsx and AaeSxl. The results revealed that knockout produced low survival and high mortality. A significant percentage of eggs (38.33%) did not hatch as compared to control groups (P value 0.00). Highest larval mortality (11.66%) was found in the knockout of Aaedsx female isoform, whereas, the emergence of only male adults also showed that the knockout of Aaedsx (female isoform) does not produce male lethality. The survival (3.33%) of knockout for AaeSxl eggs to the normal adults suggested further study to investigate AaeSxl as an efficient upstream of Aaedsx to target for sex transformation in Ae. aegypti mosquitoes.

The Antibacterial and Larvicidal Potential of Bis-(2-Ethylhexyl) Phthalate from Lactiplantibacillus plantarum.

Lactic acid bacteria produce a variety of antibacterial and larvicidal metabolites, which could be used to cure diseases caused by pathogenic bacteria and to efficiently overcome issues regarding insecticide resistance. In the current study, the antibacterial and larvicidal potential of Bis-(2-ethylhexyl) phthalate isolated from Lactiplantibacillus plantarum BCH-1 has been evaluated. Bioactive compounds were extracted by ethyl acetate and were fractionated by gradient column chromatography from crude extract. Based on FT-IR analysis followed by GC-MS and ESI-MS/MS, the active compound was identified to be Bis-(2-ethylhexyl) phthalate. Antibacterial potential was evaluated by disk diffusion against E. coli (12.33 ± 0.56 mm inhibition zone) and S. aureus (5.66 ± 1.00 mm inhibition zone). Larvicidal potency was performed against Culex quinquefasciatus Say larvae, where Bis-(2-ethylhexyl) phthalate showed 100% mortality at 250 ppm after 72 h with LC50 of 67.03 ppm. Furthermore, after 72 h the acetylcholinesterase inhibition was observed as 29.00, 40.33, 53.00, 64.00, and 75.33 (%) at 50, 100, 150, 200, and 250 ppm, respectively. In comet assay, mean comet tail length (14.18 ± 0.28 µm), tail DNA percent damage (18.23 ± 0.06%), tail movement (14.68 ± 0.56 µm), comet length (20.62 ± 0.64 µm), head length (23.75 ± 0.27 µm), and head DNA percentage (39.19 ± 0.92%) were observed at 250 ppm as compared to the control. The current study for the first time describes the promising antibacterial and larvicidal potential of Bis-(2-ethylhexyl) phthalate from Lactiplantibacillus plantarum that would have potential pharmaceutical applications.

Furanodiene: A Novel, Potent, and Multitarget Cancer-fighting Terpenoid.

Natural products have served as a limitless reservoir of bioactive scaffolds for drug discovery against several disorders. Furanodiene is a bioactive natural product isolated from several plants of genus Curcuma. Its therapeutic potential against cancer, inflammation, and angiogenesis has been well-documented. The current review is an update about the natural sources and anti-cancer action mechanism of furanodiene. Furanodiene exerts its anti-cancer effects via induction of apoptosis in several cancer types by modulating MAPKs/ERK, NF-κB, and Akt pathways. Furanodiene has been systematically studied for its anti-cancer potential. However, pharmacokinetics, pharmacodynamics, pre-clinical and clinical studies still needed to be conducted to completely validate the potential of furanodiene for the treatment of cancer.

In vitro efficacy of Azadirachta indica leaf extract against methicillin resistant Staphylococci isolated from skin infection.

In this cross-sectional study, the isolation and identification of Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Resistant S. epidermidis (MRSE) was described from skin infections (n=100). Initial isolation was done by conventional procedures followed by amplification/ sequence analysis of 16S rRNA. Methicillin resistance was determined using cefoxitin discs and resistant isolates were screened for mec-A gene followed by Minimum Inhibitory Concentrations (MIC) determination of vancomycin. In second phase, we investigated extract of Azadirachta indica leaves using Fourier Transformed Infrared Spectroscopy (FTIR-Spectroscopy) and investigated in vitro activity. Initially, total of 28 Staphylococci were identified. 16S rRNA gene sequence confirmed S. aureus (22), S. epidermidis (3) and S. saprophyticus (3) isolates. Cefoxitin discs showed (7/22) MRSA, (3/3) (MRSE) and none of the methicillin resistant S. saprophyticus. MRSA and MRSE isolates showed presence of mec-A gene. However, all isolates were sensitive to vancomycin MIC (0.5-2µg/mL) and sensitive to Linezolid. FTIR-Spectroscopy of A. indica indicated the presence of azadirachtin and nimbolinin. The mean zone of inhibition was measured 14.23±1.37 and 13.66±0.70 against MRSA and MRSE isolates, respectively. Altogether, MRSA and MRSE is significant public health concern. However, vancomycin and linezolid were found effective and extract of A. indica showed in vitro effects.

Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities.

Nature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologically active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related proteins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt proliferation and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.

Ginkgetin: A natural biflavone with versatile pharmacological activities.

Natural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-κB, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro-hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neurodegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.

Insecticidal and Genotoxic effects of some indigenous plant extracts in Culex quinquefasciatus Say Mosquitoes.

Five different weed plants viz. Convulvulus arvensis, Chenopodium murale, Tribulus terrestris, Trianthema portulacastrum, and Achyranthes aspera were investigated for their entomocidal and genotoxic effects against Culex quinquefasciatus mosquitoes. High mortality was observed at 72 hours in a dose dependent manner. Among all the tested plants, A. aspera was found highly significant which showed 100% mortality at 250 ppm after 72 hours with LC50 of 87.46, 39.08 and 9.22 ppm at 24, 48, respectively. In combination with Bacillus thuringiensis israelensis (Bti); A. aspera also caused 100% mortality at 250 ppm concentration after 72 hours (LC50 8.29 ppm). Phytochemical analysis of all the tested weed plants showed the presence of flavonoids, saponins, tannins, steroids, cardiac glycosides, alkaloids, anthrequinones and terpenoids. Random Amplification of Polymorphic DNA-Polymerase chain reaction (RAPD-PCR) and comet assay were performed to assess the genotoxic effect of A. aspera but no change in DNA profile was observed. Furthermore, FTIR showed the presence of phenolic compounds in A. aspera extract. It is suggested that certain phenolic compounds such as flavonoids modulate the enzymatic activity and, hence, cause the death of larvae of Cx. quinquefasciatus. Altogether, current study would serve as an initial step towards replacement of synthetic insecticides to plant-microbe based biopesticide against Culex mosquitoes in future.

Insecticidal, biological and biochemical response of Musca domestica (Diptera: Muscidae) to some indigenous weed plant extracts.

In the current study; insecticidal, growth regulation, oviposition deterrence and repellency of petroleum ether extracts of Azadirachta indica, Penganum harmala, Datura stramonium, Tribulus terrestris and Chenopodium murale against 2nd instar larvae of housefly was investigated. Five different concentrations (5%, 10%, 15%, 20% and 25%) were used through larval feeding and the mortality data was recorded after 24, 48 and 72 hrs. Highest mortality was induced by P. harmala (63.87%) followed by D. stramonium (62.78%), A. indica (53.84%), T. terrestris (41.86%) and C. murale (4.09%) after 72 h at 25% concentration, respectively. Increased mortality was observed with increased time duration and concentration. Longest larval duration (9.33 ±â€¯0.33 days) and pupal duration (7.33 ±â€¯0.33 days) days) was recorded in larvae treated with 25% concentration of P. harmala which also caused a decrease in the activity of AChE, ACP, AKP, α-Carboxyl, and ß-Carboxyl enzymes. However, at 25% concentration, C. murale showed highest oviposition deterrence activity (81.88%) followed by D. stramonium (79.58%). In comet assay test, at highest concentration (25%) the mean comet tail lengths represented by Penganum harmala, Datura stramonium and Azadirachta indica (Reference plant) were 10.20 ±â€¯0.49, 9.20 ±â€¯0.37 and 7.80 ±â€¯0.49 µm while percent DNA damage was 10.56 ±â€¯0.77, 10.67 ±â€¯1.62 and 8.11 ±â€¯0.85% respectively compared to controls cells. Phytochemical analysis indicated the presence of flavonoids, steroids, saponins, cardiac glycosides, tannins, alkaloids, terpenoids and anthraquinones. Fourier Transform Infrared spectroscopy (FTIR) analysis revealed the presence of phenolic flavonoids, saponins, tannins as major functional groups. Further studies are needed to explore and thus, to incorporate weed plant extracts for the management of house flies.

Effect of organic and in-organic chromium supplementation on growth performance and genotoxicity of Labeo rohita.

In aquaculture industry, the aim of feed formulation is to provide the fish with feasible diet to enhance their body. Carbohydrates supplemented with chromium compounds (organic and in-organic) are major energy currencies for biological machinery of fish. Here, this article presents a description that emphasizes the effect of chromium picolinate (organic) and chromium chloride hexahydrate (in-organic) on growth execution and genotoxicity of Labeorohita. Seven groups (each with a replica) with 30 Labeorohita fingerlings were formed: a control group, three groups were supplemented with chromium chloride Hexahydrate (0.3, 0.5 and 0.6 mg kg-1) and three groups were supplemented with Cr-Pic, 0.3, 0.5 and 0.6 mg kg-1) respectively. The experimental group T4 fortified with (Cr-Pic) along with carbohydrates by dose of 0.3 mg/kg demonstrated significant results (P < 0.05). Superior growth for Labeo rohita was observed as compared to control and other experimental groups. Minimum growth trend was observed in group T5 (CP-0.5 mg/kg), T6 (CP-0.6 mg/kg) and T7 (control) respectively. Comet assay results indicated the dose and Cr related (organic or in-organic) genetic damage in fish erythrocytes. Hence, maximum comet parameters (Tail length, Tail DNA and Olive Tail Moment) were observed in (in-organic Cr) by 0.3 mg/kg concentration. This study suggested the toxicity corresponding to in-organic Cr but organic Cr could be used as growth promoter if so. Overall results demonstrated supplementation of organic chromium compounds by 0.3 mg/kg should be reconsidered for growth. This drive of research address the fish farmers to utilize the feed supplemented with organic Cr compounds which is most appropriate to provide sustainable yield as part of increment in growth performance and beneficial health effects for consumers on indices to reduce the toxicity risks.

Molecular identification of blaCTX-M and blaTEM genes among multi-drug resistant Enteropathogenic Escherichia coli isolated from children.

In this cross sectional study (June 2016 to June 2017), we studied the isolation and molecular characterization of multi-drug resistant Escherichia coli (MDR-E. coli) from children suffering from diarrhea. For this purpose, a total of 100 fecal samples were collected with the consent of the parents/ guardians on a prescribed form. The bacterial isolation was done by employing conventional and standard microbiological procedures. Subsequently, all the isolates were identified on the basis of biochemical tests and were further characterized by amplification of 16S rRNA gene followed by di-deoxy sequencing of the amplified product. Afterwards, the isolates were subjected to antimicrobial susceptibility profiling using Kirby Bauer disc diffusion method. A total of 87 E. coli isolates were identified in the current study and majority of the isolates were found sensitive to all or few antimicrobials. However, 14 E. coli isolates were found resistance to multiple drugs including amoxicillin-clavulanic acid, ciprofloxacin, gentamicin, cefoperazone and ofloxacin, hence termed as MDR-E. coli. All of the 14 isolates were further analyzed for the identification of blaCTX-M and blaTEM genes through PCR using specific primers. This resistant was found to be associated with the presence of plasmid encoded beta lactamases genes including blaCTX-M (13/14 E. coli isolates) and blaTEM (9/14 E. coli isolates). Altogether, it was found that ESBLs harboring E. coli is potential source of diarrhea among pediatric diarrheal patients. Therefore, molecular identification and characterization of bacterial pathogens along with antimicrobial susceptibility are critical to understand MDR- E. coli infections.

Study on survival, growth, haematology and body composition of Cyprinus carpio under different acute and chronic salinity regimes.

Pakistan's most of the land is less productive or no productivity at all due to erosion and salinity of the soil, which can be utilized to develop fisheries. The project, "Survival, growth and body composition of Cyprinus carpio under different salinity regimes" was undertaken in two phases. In the first phase susceptibility of Cyprinus carpio at four salinity levels in triplicate within 0-10 g L-1NaCl for 96 h in each aquarium was checked after one week acclamation at 0 g L-1, 2 g L-1 and 4 g L-1 NaCl. LC50 values varied from 7.67 to 10.65 g L-1 after 96 h for C. carpio. Percentage mortality of the fish and important water quality parameters after every 12 h were observed for a period of 96-h. Probit analysis showed that 96-h LC50 values ranged from 7.67 to 10.65 g L-1 . During experimental period aquaria water temperature ranged from 29.6 to 33.7 °C, pH values fluctuated between 7.8 and 9.7, Electrical conductivity values ranged from 2.40 to 20.13 dSm-1 and Dissolved oxygen ranged between 2.23 and 10 mg L-1. Sub-lethal salt concentration i.e. 0 g L-1 to 3 g L-1 NaCl upto 40 days showed that growth of C. carpio decreased with the increase of water salinity levels and ceased at 4 g L-1 salinity and increase in salinity have negatively affected hematological parameters.

Efficacy of Chrozophora plicata and Trianthema portuclacastrum weed plant extracts against Trogoderma granarium Everts under laboratory conditions.

The efficacy of Chrozophora plicata and Trianthema portuclacastrum extracts was investigated against Trogoderma granarium at 10%, 20% and 30% concentrations and 2, 4 and 6 days of exposure periods. It was found that T. portuclacastrum extract caused significantly higher larval mortality (37.47%) than C. plicata (27.03%). Maximum number of T. granarium larvae (91.11% and 82.22%) was repelled when exposed to 30% concentration. A significant reduction in percentage larval emergence was also found in F1 generation. A decrease in the activity of Acetylcholine Esterase (AChE), Acid Phosphatase (ACP), Alkaline Phosphatase (AKP), α-Carboxyl and ß-Carboxyl was also found. The FTIR analysis showed the presence of polyphenolic compounds in T. portuclacastrum extract. The overall results revealed that T. portuclacastrum extract was very effective against T. granarium than C. plicata.

A Drosophila genetic screen for suppressors of S6kinase-dependent growth identifies the F-box subunit Archipelago/FBXW7.

This study was designed to identify novel negative regulators of the Drosophila S6kinase (dS6K). S6K is a downstream effector of the growth-regulatory complex mTORC1 (mechanistic-Target-of-Rapamycin complex 1). Nutrients activate mTORC1, which in turn induces the phosphorylation of S6K to promote cell growth, whereas fasting represses mTORC1 activity. Here, we screened 11,000 RNA-interfering (RNAi) lines and retained those that enhanced a dS6K-dependent growth phenotype. Since RNAi induces gene knockdown, enhanced tissue growth supports the idea that the targeted gene acts as a growth suppressor. To validate the resulting candidate genes, we monitored dS6K phosphorylation and protein levels in double-stranded RNAi-treated S2 cells. We identified novel dS6K negative regulators, including gene products implicated in basal cellular functions, suggesting that feedback inputs modulate mTORC1/dS6K signaling. We also identified Archipelago (Ago), the Drosophila homologue of FBXW7, which is an E3-ubiquitin-ligase subunit that loads ubiquitin units onto target substrates for proteasome-mediated degradation. Despite a previous report showing an interaction between Ago/FBXW7 and dS6K in a yeast two-hybrid assay and the presence of an Ago/FBXW7-consensus motif in the dS6K polypeptide, we could not see a direct interaction in immunoprecipitation assay. Nevertheless, we observed that loss-of-ago/fbxw7 in larvae resulted in an increase in dS6K protein levels, but no change in the levels of phosphorylated dS6K or dS6K transcripts, suggesting that Ago/FBXW7 indirectly controls dS6K translation or stability. Through the identification of novel negative regulators of the downstream target, dS6K, our study may help deciphering the underlying mechanisms driving deregulations of mTORC1, which underlies several human diseases.

Determination of anti-oxidative, anti-microbial activity and heavy metal contents of Leucoagaricus leucothites.

Mushrooms, a treasure of diverse bioactive scaffolds, have been widely admired due to their nutritional and medicinal significance all over the world. The current study intended to evaluate the therapeutic potentiality of an edible mushroom, Leucoagaricus leucothites (Vittad.) Wasser. Thus, anti-oxidant potential of L. leucothites was determined using DPPH assay and for the determination of anti-microbial potential agar dilution procedure was followed. TOS (total oxidant status), TAS (total anti-oxidant status), and OSI (oxidative stress index) values were evaluated utilizing Rel Assay Kits. For the assessment of heavy metal contents, wet decomposition approach with atomic absorption spectrophotometry was adopted. Screening of phytochemicals present in ethanolic extract of L. leucothites were determined by HPLC. TAS, TOS and OSI values were found to be 8.291mmol/L, 10.797µmol/L and 0.130 respectively. Our results declared that heavy metal contents are generally in the safe range. Phytochemical analysis of L. leucothites has affirmed the presence of important phenolics such as gallic acid, catechin, and hesperidin. Investigations on anti-oxidant and anti-microbial potential of L. leucothites has uncovered the fact that this naturally occurring, biologically active, and therapeutically effective mushroom specie has natural borne anti-oxidant and anti-microbial potential and it would be worthwhile to use it for nutritional as well as medicinal purpose.

Ameliorative effects of Moringa oleifera on copper nanoparticle induced toxicity in Cyprinus carpio assessed by histology and oxidative stress markers.

Nanoparticles (NPs) enter the environment mainly through waste water effluents, accidental spillage, and industrial runoffs. This is worrying because NPs can enter the human body owing to their large aspect-to-size ratio and reactive surfaces that facilitate their penetration through biological barriers and thus can induce oxidative stress in host cells. Therefore, there is a growing concern about the toxicity of NPs, which needs to be addressed. Thus, this study investigated the ameliorative effects of Moringa oleifera seed extract (MOSE) in Cyprinus carpio exposed to copper nanoparticles (Cu-NPs). For the in vivo assessment of the shielding effects of MOSE, 240 samples of C. carpio (40-45 g) were randomly allocated to 24 experimental tanks (10 fish/tank of 40 L) 24 h prior to the start of this experiment. The experimental fish were faced with the water-born exposure of a pre-determined dose of 1.5 mg Cu-NPs/l along with pre- and post-treatment with different doses (100 or 200 or 300 mg l-1) of MOSE for 28 days. The MOSE showed significant ameliorative effect on the antioxidant defense, in response to the elevated levels of Cu-NP-induced oxidative stress. It also played a protective role as indicated by the suppression of the histological alterations in the gills and liver of fish exposed to the Cu-NPs. It was concluded that the Cu-NP-induced toxicity in C. carpio was ameliorated by the use of MOSE in this study. Moreover, the post-Cu-NP treatment stage showed more protective effects of MOSE than the pre-Cu-NP treatment phase. Further studies are suggested to determine the optimum dose and delivery method of MOSE for similar or different NP exposed fish.

Efficacy of Azadirachta indica organic extracts against clinical methicillin resistant Staphylococcus aureus isolates.

In current study we investigated the efficacy of organic extracts of Azadirachta indica leaves against Methicillin Resistant Staphylococcus aureus (MRSA) clinical isolates. For this purpose fresh leaves were used to prepare ethanol, methanol and chloroform extract. Secondly, a cross sectional study was conducted to isolate MRSA in clinical samples from patients having surgical/ non-surgical wounds from Allied Hospital and District Head Quarter Hospital, Faisalabad. The S. aureus isolates were initially identified by biochemical characterization, followed by identification of MRSA using cefoxitin disc diffusion test that was finally confirmed by genomic amplification of mecA gene, responsible for resistance. All MRSA isolates were tested to find vancomycin resistant S. aureus (VRSA) using E-strips (M.I.C. EvaluatorTM, Oxide, UK). The data showed an overall 37% prevalence of S. aureus including 56.75% clinical MRSA isolates while none of the isolated S. aureus showed resistance to vancomycin. The antimicrobial activity was measured as mean zone of inhibition for each extract against all MRSA isolates and it was found as 15.38±2.26, 16.09±3.09 and 17.42±2.48 for methanol, ethanol and chloroform extracts respectively. Chloroform extract showed significantly high antimicrobial activity against MRSA isolates. Altogether, the current study exposed the high prevalence of MRSA isolates from tertiary care hospitals. However, all MRSA isolates were found susceptible to organic extracts of A. indica leaves.

Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities.

Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-ß1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCß2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1ß, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.

Toxicity, Phytochemical Composition, and Enzyme Inhibitory Activities of Some Indigenous Weed Plant Extracts in Fruit Fly, Drosophila melanogaster.

Drosophila melanogaster being used as model organism is considered as pest of homes, restaurants, and fruit markets. The damaged fruits are also reported to serve as a carrier for various diseases. The current study was designed to evaluate the toxicity of petroleum extract of some weed plants, namely, Euphorbia prostrata, Parthenium hysterophorus, Fumaria indica, Chenopodium murale, and Azadirachta indica, against D. melanogaster. Mortality at 10, 20, and 30% concentrations after 24 and 48 hours was found comparatively low. E. prostrata caused high mortality (51.64%) at 30% concentration and was found more toxic (LC50 27.76; P value 0.00) after 72 hours. A. indica showed high LC50 value (P value 0.15) compared to other weed plants. The combination of E. prostrata and Bti showed highest mortality (100%; LC50 12.49; P value 0.00) after 72 hours. Similarly, the same combination caused maximum reduction in the activity of AChE, AcP, AkP, α-Carboxyl, and ß-Carboxyl enzymes. Phytochemical analysis showed the presence of flavonoids, saponins, tannins, steroids, cardiac glycosides, alkaloids, anthraquinones, and terpenoids. FTIR analysis of E. prostrata showed the presence of phenolic compounds. It is suggested that further studies are needed in order to incorporate weed plant extracts in combination with Bti for the management of fruit flies.

Sorafenib tosylate, Ribavirn and Sofosbuvir combination therapy for HCV virus infected patients with decompensated liver cancer.

Hepatitis C is the most common health problem worldwide and is major cause of death due to proliferation of hepatocellular carcinoma. The medicines available for HCV treatment overcome up-to 95% complications of HCV. However, liver cancer needs some additional care. Normally Sorafenib tosylate 200 mg is recommended for liver cancer. There is no such trial in which this drug could effectively be used in combination of direct acting antivirals for HCV. The study was conducted for HCV patients (n=30) with liver cancer having decompensated stage. Combination of Sorafenib tosylate, Ribavirn and Sofosbuvir were used for the pharmacokinetics of these medicines. Child pugh score less then 7 (CP A) in adults during treatment phase (received 12 weeks of Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir 400 mg once daily) have no side effect while child pugh score 7-9 (CP B) have evidence of hypertension. The main efficiency end point sustained virology response with overcoming liver cancer as well in 12 weeks after end treatment (SVR-LLC 12). Mean pharmacokinetic exposure to Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir at week 8th was 2.1, 1.5,1.2 times greater in CP B than in CP A. Adverse effects (AEs) were observed in 12 out of 30 patients but not severe as lethal for life. Treatment with Sorafenib tosylate, Ribavirn and Sofosbuvir for twelve weeks was harmless and well accepted, 100 % patients achieve (SVR LLC 12) with 10-fold cure rate more than previous ones. The combination therapy of Sorafenib tosylate, Ribavirn and Sofosbuvir was found helpful for the management of decompensated liver cancer.

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities.

Fraxinus, a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications.