Prevalence of crimean Congo hemorrhagic fever in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: CCHFV is well recognized as a major public health threat and its prevalence and epidemiological distribution in Pakistan and specifically in KP province is not well documented. METHODS: We used a gold-standard PCR-based diagnostic assay for confirmation of CCHFV among suspected patients. A total of 150 patients were enrolled from June 2022 to September 2022 and their blood samples were collected for PCR confirmation. RESULTS: The overall positivity rate for CCHFV was 26.67 %, with the virus mostly prevalent in the middle-aged group (21-40 years). In the July of 2022, a significant spike in the prevalence of CCHFV was observed in provincial capital Peshawar with the highest burden (31.57 %). CONCLUSION: Our findings indicate the necessity of strengthening CCHFV monitoring programs and intensifying efforts to identify hotspot regions for effective surveillance and control of CCHFV. The months before the Eid-ul-Adha are crucial in the context of CCHFV control.

Insight into the molecular mechanism, cytotoxic, and anticancer activities of phyto-reduced silver nanoparticles in MCF-7 breast cancer cell lines.

This contribution insight on the cytotoxic and anticancer activities and molecular mechanism of phyto-reduced silver nanoparticles (AgNPs) in MCF-7 breast cancer cell lines. A simple, entirely green synthesis process was optimized for the phyto-reduction of AgNP (~12.7 nm) using aqueous leaf extracts of Indigofera heterantha. The structural and vibrational properties of biosynthesized AgNPs were extensively characterized using UV-Vis spectrophotometer, x-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform Infrared spectroscopy (FTIR), while their shape and morphology was studied through scanning electron microscopy (SEM). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay indicates concentration dependent inhibition with IC50 , 27.93 ± 2.10 µg/mL against MCF-7 cells and 294.38 ± 3.87 µg/mL against L929 cells. The manifested anticancer mechanism in MCF-7 cells was extensively studied using Acridine orange/ethidium bromide (AO/EB), 4',6-diamidino-2-phenylindole (DAPI) and Annexin-V/propedium iodide fluorescence microscopic assays. The level of reactive oxygen species (ROS) was measured using DCFH-DA fluorescent spectroscopy. Overall, the results show that AgNPs exhibit cytotoxic and apoptotic effect on breast cancer MCF-7 cells by damaging membrane integrity and nuclear fragmentation due to oxidative stress generated by elevated level of ROS. RESEARCH HIGHLIGHTS: Biomimetic synthesis of nano dimension size silver nanoparticles (AgNPs). Characterization of AgNPs through UV-Vis, DLS, XRD, FTIR, and SEM. Cytotoxic and anticancer effects of the biosynthesized AgNPs in L929 fibroblast cells and MCF7 breast cancer respectively. Determination of morphological, and nuclear changes triggered by AgNPs in MCF 7 breast cancer cells using fluorescent microscopy and flow cytometry. Apoptosis induction by AgNPs in cancer cells through oxidative stress generated by reactive oxygen species (ROS).

Preliminary insights on the mutational spectrum of BRCA1 and BRCA2 genes in Pakhtun ethnicity breast cancer patients from Khyber Pakhtunkhwa (KP), Pakistan.

Gene mutations are a source of genetic instability which fuels the progression of cancer. Mutations in BRCA1 and BRCA2 are considered as major drivers in the progression of breast cancer and their detection indispensable for devising therapeutic and management approaches. The current study aims to identify novel pathogenic and recurrent mutations in BRCA1 and BRCA2 in Pakhtun population from the Khyber Pakhtunkhwa. To determine the BRCA1 and BRCA2 pathogenic mutation prevalence in Pakhtun population from KP, whole exome sequencing of 19 patients along with 6 normal FFPE embedded blocks were performed. The pathogenicity of the mutations were determined and they were further correlated with different hormonal, sociogenetic and clinicopathological features. We obtained a total of 10 mutations (5 somatic and 5 germline) in BRCA1 while 27 mutations (24 somatic and 3 germline) for BRCA2. Five and seventeen pathogenic or deleterious mutations were identified in BRCA1 and BRCA2 respectively by examining the mutational spectrum through SIFT, PolyPhen-2 and Mutation Taster. Among the SNVs, BRCA1 p.P824L, BRCA2 p. P153Q, p.I180F, p.D559Y, p.G1529R, p.L1576F, p.E2229K were identified as mutations of the interaction sites as predicted by the deep algorithm based ISPRED-SEQ prediction tool. SAAFEQ-SEQ web-based algorithm was used to calculate the changes in free energy and effect of SNVs on protein stability. All SNVs were found to have a destabilizing effect on the protein. ConSurf database was used to determine the evolutionary conservation scores and nature of the mutated residues. Gromacs 4.5 was used for the molecular simulations. Ramachandran plots were generated using procheck server. STRING and GeneMania was used for prediction of the gene interactions. The highest number of mutations (BRCA1 7/10, 70 %) were on exon 9 and (BRCA2, 11/27; 40 %) were on exon 11. 40 % and 60 % of the BRCA2 mutations were associated Grade 2 and Grade 3 tumors respectively. The present study reveals unique BRCA1 and BRCA2 mutations in Pakhtun population. We further suggest sequencing of the large cohorts for further characterizing the pathogenic mutations.

Mutational Landscape and In-Silico Analysis of TP53, PIK3CA, and PTEN in Patients with Breast Cancer from Khyber Pakhtunkhwa.

Herein, we report the mutational spectrum of three breast cancer candidate genes (TP53, PIK3CA, and PTEN) using WES for identifying potential biomarkers. The WES data were thoroughly analyzed using SAMtools for variant calling and identification of the mutations. Various bioinformatic tools (SIFT, PolyPhen-2, Mutation Taster, ISPRED-SEQ, SAAFEQ-SEQ, ConSurf, PROCHECK etc.) were used to determine the pathogenicity and nature of the SNVs. Selected interaction site (IS) mutations were visualized in PyMOL after building 3D structures in Swiss-Model. Ramachandran plots were generated by using the PROCHECK server. The selected IS mutations were subjected to molecular dynamic simulation (MDS) studies using Gromacs 4.5. STRING and GeneMANIA were used for the prediction of gene-gene interactions and pathways. Our results revealed that the luminal A molecular subtype of the breast cancer was most common, whereas a high percentage of was Her2 negatives. Moreover, the somatic mutations were more common as compared to the germline mutations in TP53, PIK3CA, and PTEN. 20% of the identified mutations are reported for the first time from Khyber Pakhtunkhwa. In the enrolled cohort, 23 mutations were nonsynonymous SNVs. The frequency of mutations was the highest in PIK3CA, followed by TP53 and PTEN. A total of 13 mutations were found to be highly pathogenic. Four novel mutations were identified on PIK3CA and one each on PTEN and TP53. SAAFEQ-SEQ predicted the destabilizing effect for all mutations. ISPRED-SEQ predicted 9 IS mutations (6 on TP53 and 3 on PIK3CA), whereas no IS mutation was predicted on PTEN. The TP53 IS mutations were TP53R43H, TP53Y73X, TP53K93Q, TP53K93R, TP53D149E, and TP53Q199X; whereas for PIK3CA, the IS mutations were PIK3CAL156V, PIK3CAM610K, and PIK3CAH1047R. Analysis from the ConSurf Web server revealed five SNVs with a highly conserved status (conservation score 9) across TP53 and PTEN. TP53P33R was found predominant in the grade 3 tumors, whereas PTENp.C65S was distributed on ER+, ER-, PR+, PR-, Her2+, and Her2- patients. TP53p.P33R mutation was found to be recurring in the 14/19 (73.6%) patients and, therefore, can be considered as a potential biomarker. Finally, these mutations were studied in the context of their potential association with different hormonal and social factors.

Phyto-fabrication of ultrafine nanoscale holmium oxide HT-Ho2O3 NPs and their biomedical potential.

In this study holmium oxide nanoparticles (Ho2O3 NPs) are fabricated using Hyphaene thebaica extracts as a bioreductant. The XRD pattern of HT-Ho2O3 NPs (product from phyto-reduction) suggested that the nanoparticles are crystalline with no impurities. Scherrer approximation revealed grain sizes of ∼10 nm. The HR-TEM revealed HT-Ho2O3 NPs possessed a quasi-spherical morphology complemented by SEM and the particle sizes were in the range of 6-12 nm. The infrared spectra revealed characteristic Ho-O bonding at ∼603 cm-1. Raman spectra indicated five main peaks positioned at 156 cm-1, 214 cm-1, 328 cm-1, 379 cm-1 and 607 cm-1. Eg (optical bandgap) was found to be 5.1 eV. PL spectra indicated two major peaks at 415 nm and 607 nm. EDS spectra confirmed the elemental presence of holmium (Ho). Spotty rings were obtained during the SAED measurement which indicated crystallinity of HT-Ho2O3 NPs. The HT-Ho2O3 NPs were further analyzed for their antioxidant, anti-angiogenic and cytotoxic properties. The antioxidant potential was moderate i.e., 43.40 ± 0.96% at 1000 µg mL-1 which decreased in a dose dependent manner. Brine shrimp lethality was highest at 1000 µg mL-1 with the LC50 320.4 µg mL-1. Moderate anti-angiogenic potential was observed using in ova CAM assay. MTT bioassay revealed that the HT-Ho2O3 NPs inhibited the 3T3 cells (IC50 67.9 µg mL-1), however, no significant inhibition was observed against MCF-7 cells. α-Amylase and ß-glucosidase inhibition revealed that the HT-Ho2O3 NPs can be of use in controlling blood glucose levels. Overall, it can be concluded that biosynthesis using aqueous extracts can be a suitable alternative in finding ecofriendly paradigms for the synthesis of nanoparticles. We suggest extended research into the bioreduced Ho2O3 NPs for establishing their biomedical potential and toxicity.

Valorization and Repurposing of Citrus limetta Fruit Waste for Fabrication of Multifunctional AgNPs and Their Diverse Nanomedicinal Applications.

Herein we propose an ecofriendly process for the biofabrication of AgNPs by applying fruit waste of Citrus limetta. The aqueous extracts from the peels of the fruit were used as green chelating and stabilizing agents. Structural, optical, vibrational, morphological, and magnetic properties were established using UV-Vis (ultraviolet visible spectroscopy), XRD (X-rays diffraction), FTIR (Fourier transformed infrared spectroscopy), EDS (energy dispersive spectroscopy), SEM (scanning electron microscopy), ESR (electron spin resonance), and PPMS (physical property management system), while the thermal properties were established using TGA/DTG (thermal gravimetric analysis/derivative thermogravimetry). XRD pattern revealed intense peaks with single-phase purity, while the Debye-Scherrer approximation revealed an average crystallite size of 33.18 nm. The W-H plot revealed the size of 55.2 nm and strain 2.68 × 10-4. FTIR spectra revealed the involvement of different functional groups and major IR vibrations were observed at 2329 cm-1, 2092 cm-1, 1794 cm-1, 1268 cm-1, and 754 cm-1. TGA/DTG revealed major weight loss events at 240 °C and 360 °C. SEM revealed spherical or quasi-spherical morphology, while EDS confirmed the presence of elemental silver. The M-H behavior for all measurement temperature shows diamagnetic behavior. Electron spin resonance (ESR) revealed a high proportion of free electrons. Furthermore, the pharmacognostic and nanomedicinal potential CL-AgNPs was established using multiple in vitro and in vivo bioassays. The in vivo wound healing assays in mice revealed excellent healing potential which were similar to positive control. The percent wound healing is reported to be 93% on the 14th day of incision after application of CL-AgNPs. Bioassays were performed to assess enzyme inhibition potential of the CL-AgNPs for Alzheimer disease and antidiabetic applications. The AChE and BChE potential of the CL-AgNPs was highest at 1000 µg mL-1, i.e., 92% and 56%, respectively. The α-glucosidase inhibition potential for the CL-AgNPs was higher as compared to the α-glucosidase, while the DPPH free radical scavenging was reported to be 70% to 11% at varying concentrations between 1000 and 62.5 µg mL-1. Overall, our results indicate that the waste fruit peels can be a sustainable and eco-friendly resource of synthesis of the multifunctional nanoparticles.

Physicochemical and nanomedicine applications of phyto-reduced erbium oxide (Er2O3) nanoparticles.

Hyphaene thebaica fruits were used for the fabrication of spherical erbium oxide nanoparticles (HT-Er2O3 NPS) using a one-step simple bioreduction process. XRD pattern revealed a highly crystalline and pure phase with crystallite size of ~ 7.5 nm, whereas, the W-H plot revealed crystallite size of 11 nm. FTIR spectra revealed characteristic Er-O atomic vibrations in the fingerprint region. Bandgap was obtained as 5.25 eV using K-M function. The physicochemical and morphological nature was established using Raman spectroscopy, reflectance spectroscopy, SAED and HR-TEM. HT-Er2O3 NPS were further evaluated for antidiabetic potential in mice using in-vivo and in-vitro bioassays. The synthesized HT-Er2O3 NPS were screened for in vitro anti-diabetic potentials against α-glucosidase enzyme and α-amylase enzyme and their antioxidant potential was evaluated using DPPH free radical assay. A dose dependent inhibition was obtained against α-glucosidase (IC50 12 µg/mL) and α-amylase (IC50 78 µg/mL) while good DPPH free radical scavenging potential (IC50 78 µg mL-1) is reported. At 1000 µg/mL, the HT-Er2O3 NPS revealed 90.30% and 92.30% inhibition of α-amylase and α-glucosidase enzymes. HT-Er2O3 NPs treated groups were observed to have better glycemic control in diabetic animals (503.66 ± 5.92*** on day 0 and 185.66 ± 2.60*** on day 21) when compared with positive control glibenclamide treated group. Further, HT-Er2O3 NPS therapy for 21 days caused a considerable effect on serum total lipids, cholesterol, triglycerides, HDL and LDL as compared to untreated diabetic group. In conclusion, our preliminary findings on HT-Er2O3 NPS revealed considerable antidiabetic potential and thus can be an effective candidate for controlling the post-prandial hyperglycemia. However, further studies are encouraged especially taking into consideration the toxicity aspects of the nanomaterial.

Green Nano-Biotechnology: A New Sustainable Paradigm to Control Dengue Infection.

Dengue is a growing mosquito-borne viral disease prevalent in 128 countries, while 3.9 billion people are at high risk of acquiring the infection. With no specific treatment available, the only way to mitigate the risk of dengue infection is through controlling of vector, i.e., Aedes aegypti. Nanotechnology-based prevention strategies like biopesticides with nanoformulation are now getting popular for preventing dengue fever. Metal nanoparticles (NPs) synthesized by an eco-friendly process, through extracts of medicinal plants have indicated potential anti-dengue applications. Green synthesis of metal NPs is simple, cost-effective, and devoid of hazardous wastes. The recent progress in the phyto-synthesized multifunctional metal NPs for anti-dengue applications has encouraged us to review the available literature and mechanistic aspects of the dengue control using green-synthesized NPs. Furthermore, the molecular bases of the viral inhibition through NPs and the nontarget impacts or hazards with reference to the environmental integrity are discussed in depth. Till date, major focus has been on green synthesis of silver and gold NPs, which need further extension to other innovative composite nanomaterials. Further detailed mechanistic studies are required to critically evaluate the mechanistic insights during the synthesis of the biogenic NPs. Likewise, detailed analysis of the toxicological aspects of NPs and their long-term impact in the environment should be critically assessed.

Microbes-mediated synthesis strategies of metal nanoparticles and their potential role in cancer therapeutics.

Past few years have seen a paradigm shift towards ecofriendly, green and biological fabrication of metal nanoparticles (MNPs) for diverse nanomedicinal applications especially in cancer nanotheranostics. Besides, the well-known green synthesis methods of plant materials, the potential of the microbial world (bacteria, fungi, alga, etc.) in biofabrication is equally realized. Biomolecules and enzymes in the microbial cells are capable of catalyzing the biosynthesis process. These microbial derived inorganic nanoparticles have been frequently evaluated as potential agents in cancer therapies revealing exciting results. Through, cellular and molecular pathways, these microbial derived nanoparticles are capable of killing the cancer cells. Considering the recent developments in the anticancer applications of microbial derived inorganic MNPs, a dire need was felt to bring the available information to a single document. This manuscript reviews not only the mechanistic aspects of the microbial derived MNPs but also include the diverse mechanisms that governs their anticancer potential. Besides, an updated literature review is presented that includes studies of 2019-onwards.

Extraction optimization, Total Phenolic-Flavonoids content, HPLC-DAD finger printing, antimicrobial, antioxidant and cytotoxic potentials of Chinese folklore Ephedra intermedia Schrenk & C. A. Mey

Abstract Plants from genus Ephedra are commonly used by the Chinese people as folk medicine for treatment of various diseases. The current study was designed to explore the ethno-pharmacological based pharmacological potentials of Ephedra intermedia Schrenk & C.A. Mey. (E. intermedia). Plant aerial parts were extracted using ten solvent systems with increasing order of polarity. Samples were analyzed for total phenolic and flavonoid contents, HPLC-DAD analysis, antibacterial, antifungal, HepG2 cell line cytotoxicity, hemolysis and antioxidant potentials following standard procedures. Highest percent extract recovery was observed in Eth+WT (25.55 % w/w) solvent system. Flavonoid and phenolic contents were higher in chloroform and Met+WT fractions respectively. Considerable antibacterial activity was shown by Eth+Met extract against B. subtilis and K. pneumonia (MIC of 11.1μg/mL for each). Eth extract exhibited high antifungal activity against A. fumigates (15±0.31 mm DIZ). Met+WT extract showed significant cytotoxicity against HepG2 cell lines with IC50 of 13.51+0.69 μg/mL. Substantial free radical scavenging activity (74.9%) was observed for Met+Eth extract. In the current study, several solvent systems were used for more effective extraction of fractions and can be useful in the isolation of phytochemicals. Various fractions exhibited considerable antimicrobial, antioxidant and cytotoxic potentials. Biological potentials of E. intermedia signify its potential uses in microbial, cancer and degenerative disorders and thus warrant further detailed studies.

Genus Viburnum: Therapeutic Potentialities and Agro-Food-Pharma Applications.

The genus Viburnum (Adoxaceae, Dipsacales) is of scientific interest due to the chemical components and diverse biological activities found across species of the genus, which includes more than 230 species of evergreen, semievergreen, or deciduous shrubs and small trees. Although frequently used as an ornament, the Viburnum species show biological properties with health-promoting effects. Fruits, flowers, and barks of certain species are used for pharmaceutical purposes or as cooking ingredients, hence containing biochemical compounds with health-promoting activity such are carotenoids, polyphenols, and flavonoids. However, its taxonomical determination is difficult, due to its wide distribution and frequent hybridizations; therefore, an objective classification would allow us to understand its biological activity based on its phytochemical components. More than sixty phytochemical compounds have been reported, where vibsanin-type diterpenes and their derivatives are the most prevalent. Leaves and twigs of V. dilatatum contain the largest number of phytochemicals among the genus. Through preclinical evidence, this study provides insight regarding antioxidant, antibacterial, anti-inflammatory, cytotoxic, and anticancer activities of genus Viburnum.

Silver nanoparticles biosynthesized from secondary metabolite producing marine actinobacteria and evaluation of their biomedical potential.

Biosynthesis of silver nanoparticles (AgNPs) from marine actinobacteria offers a promising avenue for exploring bacterial extracts as reducing and stabilizing agents. We report extracellular extracts of Rhodococcus rhodochrous (MOSEL-ME29) and Streptomyces sp. (MOSEL-ME28), identified by 16S rRNA gene sequencing for synthesis of AgNPs. Ultrafine silver nanoparticles were biosynthesized using the extracts of R. rhodochrous and Streptomyces sp. and their possible therapeutic applications were studied. The physicochemical properties of nanoparticles were established by HR-SEM/TEM, SAED, UV-Vis, EDS, XRD, and FTIR. UV-Vis spectra displayed characteristic absorption at 430 nm and 412 nm for AgNPs from Streptomyces sp. (S-AgNPs) and Rhodococcus sp. (R-AgNPs), respectively. HR-SEM/TEM, XRD, EDS analysis confirmed the spherical shape, crystalline nature, and elemental formation of silver. Crystallite or grain size was deduced as 5.52 nm for R-AgNPs and 35 nm for S-AgNPs. Zeta-potential indicated electrostatic negative charge for AgNPs, while FTIR revealed the presence of diverse functional groups. Disc diffusion assay indicated the broad-spectrum antibacterial potential of S-AgNPs with the maximum inhibition of B. subtilis while R-AgNPs revealed potency against P. aeruginosa at 10 µg/mL concentration. Biogenic AgNPs revealed antileishmanial activity and the IC50 was calculated as 164 µg/mL and 184 µg/mL for R-AgNPs and S-AgNPs respectively. Similarly, the R-AgNPs and S-AgNPs revealed anti-cancer potential against HepG2 and the IC50 was calculated as 49 µg/mL and 69 µg/mL for R-AgNPs and S-AgNPs, respectively. Moreover, the antioxidant activity showed significant results. MTT assay on RD cells, L20B cells, and Hep-2C indicated intensification in viability by reducing the concentration of R-AgNPs and S-AgNPs. The R-AgNPs and S-AgNPs inhibited sabin-like poliovirus (1TCID50 infection in RD cells). Furthermore, hemocompatibility at low concentrations has been confirmed. Hence, it is concluded that biogenic-AgNPs has the potential to be used in diverse biological applications and that the marine actinobacteria are an excellent resource for fabrication of AgNPs.

Precursor effects on the physical, biological, and catalytic properties of Fagonia indica Burm.f. mediated zinc oxide nanoparticles.

We report a facile, green and precursor-based comparative study on the biosynthesis of zinc oxide (ZnO) nanoparticles (NPs) using anticancerous Fagonia indica as effective chelating agent. Biosynthesis was carried out using zinc sulfate and zinc acetate as precursor salts to make ZnOS and ZnOA NPs under similar experimental conditions which were characterized extensively for physical and biological properties. Scherrer equation deduced a mean crystallite size of ~23.4 nm for ZnOA NPs and ~41 nm for ZnOS NPs. The nature of the NPs was compared using UV, diffuse reflectance spectra, Fourier transform infrared spectroscopy, thermogravimetric analysis-DTA, selected area electron diffraction, EDS, zeta potential, high resolution (HR)-SEM, and HR-TEM. Detailed in vitro pharmacognostic activities revealed a significant therapeutic potential for ZnOA and ZnOS . Potential antimicrobial activities for the NPs and their nanocosmeceutical formulations are reported. ZnOA NPs were more cytotoxic to Leishmania tropica as compared to ZnOS . Significant antioxidant and protein kinase inhibition was obtained. The hemolytic assay indicated a hemocompatible nature of both ZnOA and ZnOS NPs. Catalytic degradation of crystal violet dye (CVD) by NPs was examined under different parameters (light, dark, UV). Furthermore, sonophotocatalytic degradation of CVD was also studied. Our results suggested that precursor can have a significant effect on the physical, biological, and catalytic properties of the NPs. In future, we recommend different other in vitro, in vivo biological activities, and mechanistic studies of these as-synthesized NPs.

Floral extracts-mediated green synthesis of NiO nanoparticles and their diverse pharmacological evaluations.

Biosynthesis has emerged as an exciting interface for assembling multifunctional metal oxide nanoparticles for diverse medicinal applications. Herein, biogenic nickel oxide (NiO-NPs) is synthesized by using floral extracts of Callistemon viminalis (C. viminalis) as a low cost, ecofriendly reducing and stabilizing agent. NiO-NPs were annealed at 300 °C, 400 °C and 500 °C while their physiochemical properties were established by HR-SEM/TEM, UV, XRD, FTIR, EDS, SAED and SQUID techniques. Particle size of NiO-NPs decreased with increase in annealing temperatures. Magnetization curves indicated superparamagnetic behavior of the biogenic NiO-NPs at 300 K. Highly crystalline NiO-NPs obtained after annealing at 500 °C were used for biomedical applications. The anti-leishmanial activity on Leishmania tropica promastigotes (KMH-23) and anticancer activity on HepG2 (RCB1648) revealed excellent inhibition potential with IC50 of 37.21 µg/mL and 47 µg/mL, respectively. Significant antibacterial effect was observed against Klebsiella pneumonia and Proteus vulgaris with MIC's of 12.5 µg/mL each. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase inhibitory potential were comparable with positive control drugs. Moderate antioxidant activities were observed. NiO-NPs were observed to be hemolytic (30%) at higher dose (1000 µg/mL). Overall, NiO-NPs revealed a multifunctional nature that can be explored for diverse biomedical applications.Communicated by Ramaswamy H. Sarma.

Ethics, pandemic and environment; looking at the future of low middle income countries.

COVID-19 which started in Wuhan, China and swiftly expanded geographically worldwide, including to Low to Middle Income Countries (LMICs). This in turn raised numerous ethical concerns in preparedness, knowledge sharing, intellectual property rights, environmental health together with the serious constraints regarding readiness of health care systems in LMICs to respond to this enormous public health crisis. From the restrictions on public freedom and burgeoning socio-economic impacts to the rationing of scarce medical resources, the spread of COVID-19 is an extraordinary ethical dilemma for resource constrained nations with less developed health and research systems. In the current crisis, scientific knowledge and technology has an important role to play in effective response. Emergency preparedness is a shared responsibility of all countries with a moral obligation to support each other. This review discusses the ethical concerns regarding the national capacities and response strategies in LMICs to deal with the COVID-19 pandemic as well as the deep link between the environment and the increasing risk of pandemics.

Green-Synthesized Silver Nanoparticles Induced Apoptotic Cell Death in MCF-7 Breast Cancer Cells by Generating Reactive Oxygen Species and Activating Caspase 3 and 9 Enzyme Activities.

Silver nanoparticles are among the most significant diagnostic and therapeutic agents in the field of nanomedicines. In the current study, the green chemistry approach was made to optimize a cost-effective synthesis protocol for silver nanoparticles from the aqueous extract of the important anticancer plant Fagonia indica. We investigated the anticancer potential and possible involvement of AgNPs in apoptosis. The biosynthesized AgNPs are stable (zeta potential, -16.3 mV) and spherical with a crystal size range from 10 to 60 nm. The MTT cell viability assay shows concentration-dependent inhibition of the growth of Michigan Cancer Foundation-7 (MCF-7) cells (IC50, 12.35 µg/mL). In addition, the fluorescent microscopic analysis shows activation of caspases 3 and 9 by AgNPs that cause morphological changes (AO/EB assay) in the cell membrane and cause nuclear condensation (DAPI assay) that eventually lead to apoptotic cell death (Annexin V/PI assay). It was also observed that AgNPs generate reactive oxygen species (ROS) that modulate oxidative stress in MCF-7 cells. This is the first study that reports the synthesis of a silver nanoparticle mediated by Fagonia indica extract and evaluation of the cellular and molecular mechanism of apoptosis.

Phyto-fabricated Cr2O3 nanoparticle for multifunctional biomedical applications.

Aim: The biosynthesis of chromium oxide nanoparticles (Cr2O3 NPs), using Hyphaene thebaica as a bioreductant, for assessment of their potential nanomedicinal applications. Materials & methods: Biosynthesized Cr2O3 NPs were characterized by x-ray diffraction, Fourier-transform infrared spectroscopy, energy dispersive x-ray spectroscopy, scanning and transmission electron microscopy, selected area electron diffraction, UV-Vis spectroscopy and ζ-potential measurement. In vitro assays were used to assess the biological properties of Cr2O3 NPs. Results: Nanoparticles with size approximately 25-38 nm were obtained with a characteristic Cr-O vibration at 417 cm-1. A broad spectrum antimicrobial potential and antioxidant nature is reported. Slight inhibition of polio virus and biocompatibility at low doses was observed. Conclusion: We conclude a multifunctional nature of biogenic Cr2O3 NPs.

Bio-redox potential of Hyphaene thebaica in bio-fabrication of ultrafine maghemite phase iron oxide nanoparticles (Fe2O3 NPs) for therapeutic applications.

Maghemite (Fe2O3-NPs) nanoparticles were synthesized by a convenient, green and cost effective method using aqueous fruit extracts of Hyphaene thebaica. Different techniques like FTIR, XRD, UV-Vis, Raman, HR-TEM, EDS. SAED, Zeta potential were used to establish the nature of Fe2O3-NPs, while the therapeutic properties were studied using different biological assays including antiviral, antibacterial, antifungal, antioxidant and enzyme inhibition assays. XRD pattern revealed sharp peaks and a crystalline nature of Fe2O3-NPs. HR-TEM revealed quasi-spherical and cuboidal morphologies, while the particle size in ~10 nm. FTIR indicated a sharp peak centered at ~444 cm-1 which is the characteristic FeO band vibration. SAED pattern indicated the crystalline nature while EDS also confirmed the synthesis of Fe2O3 NPs. Zeta potential was obtained in different solvents and physiological buffers indicating highest value in water (-26.5 mV) and lowest in DMSO (-15.8 mV). Tested bacterial strains, Bacillus subtilis was found to be inhibited significantly. Aspergillus flavus appeared to be susceptible to all of the tested concentration of Fe2O3 NPs. Maximum 40.78% FRSA was obtained at 400 µg/mL. Cell culture based studies on RD cells and L20B cells indicated reduction in viability of cells with increase concentration of Fe2O3 NPs. Moderate inhibition of polio virus-1 and polio virus-2 was observed, after culturing the virus in the L20B cells. Excellent Protein Kinase (PK) inhibition was revealed. Hemolytic potential and cytotoxic potential was indicated to be dose dependent. In conclusion, the present report for the first time reports the synthesis of Fe2O3 NPs from H. thebaica fruits and reveals their biomedical potential including antiviral potential.

Persicaria hydropiper (L.) Delarbre: A review on traditional uses, bioactive chemical constituents and pharmacological and toxicological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Various plant parts of Persicaria hydropiper (L.) Delarbre (Syn.: Polygonum hydropiper L., Family: Polygonaceae) are used in traditional medicine systems as astringent, sedative, antiseptic and also for the treatment of respiratory disorders, edema and snake bites. It is also used as a spice in many Asian countries. AIM OF THE REVIEW: The main aim of this review is to critically analyze the reported traditional uses, bioactive chemical constituents and pharmacological activities of P. hydropiper. MATERIALS AND METHODS: Scientific database including PubMed, Scopus, SciFinder and secondary resources including books and proceedings were searched using relevant terminologies related to P. hydropiper and available scientific information was critically analyzed. RESULTS: Analysis of the scientific literature regarding the traditional uses revealed that P. hydropiper is used as a medicine and as spice in food preparations in various parts of the world. Various compounds including flavonoids, phenylpropanoid derivatives, and sesquiterpenoids among others were reported as active compounds. The extracts and compounds from P. hydropiper showed diverse biological activities including anti-inflammatory, antioxidant, cytotoxic, antimicrobial activities, etc. CONCLUSION: Although various research reports showed diverse biological activities for extracts and compounds obtained from P. hydropiper, very few studies were performed using animal models. Many of these studies also lacked proper experimental setting such as use of positive and negative controls and selection of dose as in most of these studies very high doses of extracts were administered. Further, as P. hydropiper is widely used in the treatment of snake bites and insect bites, such effects of extracts and/or compounds are not well explored. Future studies on P. hydropiper should be focused to establish the links between the traditional uses, active compounds and reported pharmacological activities.

Phytosynthesis of BiVO4 nanorods using Hyphaene thebaica for diverse biomedical applications.

Biosynthesis of bismuth vanadate (BiVO4) nanorods was performed using dried fruit extracts of Hyphaene thebaica as a cost effective reducing and stabilizing agent. XRD, DRS, FTIR, zeta potential, Raman, HR-SEM, HR-TEM, EDS and SAED were used to study the main physical properties while the biological properties were established by performing diverse assays. The zeta potential is reported as - 5.21 mV. FTIR indicated Bi-O and V-O vibrations at 640 cm-1 and 700 cm-1/1120 cm-1. Characteristic Raman modes were observed at 166 cm-1, 325 cm-1 and 787 cm-1. High resolution scanning and transmission electron micrographs revealed a rod like morphology of the BiVO4. Bacillus subtilis, Klebsiella pneumonia, Fusarium solani indicated highest susceptibility to the different doses of BiVO4 nanorods. Significant protein kinase inhibition is reported for BiVO4 nanorods which suggests their potential anticancer properties. The nanorods revealed good DPPH free radical scavenging potential (48%) at 400 µg/mL while total antioxidant capacity of 59.8 µg AAE/mg was revealed at 400 µg/mL. No antiviral activity is reported on sabin like polio virus. Overall excellent biological properties are reported. We have shown that green synthesis can replace well established processes for synthesizing BiVO4 nanorods.