COVID-19: A Global Challenge with Old History, Epidemiology and Progress So Far.

Humans have witnessed three deadly pandemics so far in the twenty-first century which are associated with novel coronaviruses: SARS, Middle East respiratory syndrome (MERS), and COVID-19. All of these viruses, which are responsible for causing acute respiratory tract infections (ARTIs), are highly contagious in nature and/or have caused high mortalities. The recently emerged COVID-19 disease is a highly transmittable viral infection caused by another zoonotic novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to the other two coronaviruses such as SARS-CoV-1 and MERS-CoV, SARS-CoV-2 is also likely to have originated from bats, which have been serving as established reservoirs for various pathogenic coronaviruses. Although, it is still unknown how SARS-CoV-2 is transmitted from bats to humans, the rapid human-to-human transmission has been confirmed widely. The disease first appeared in Wuhan, China, in December 2019 and quickly spread across the globe, infected 48,539,872 people, and caused 1,232,791 deaths in 215 countries, and the infection is still spreading at the time of manuscript preparation. So far, there is no definite line of treatment which has been approved or vaccine which is available. However, different types of potential vaccines and therapeutics have been evaluated and/or are under clinical trials against COVID-19. In this review, we summarize different types of acute respiratory diseases and briefly discuss earlier outbreaks of coronaviruses and compare their occurrence and pathogenicity with the current COVID-19 pandemic. Various epidemiological aspects of COVID-19 such as mode of spread, death rate, doubling time, etc., have been discussed in detail. Apart from this, different technical issues related to the COVID-19 pandemic including use of masks and other socio-economic problems associated with the pandemic have also been summarized. Additionally, we have reviewed various aspects of patient management strategies including mechanism of action, available diagnostic tools, etc., and also discussed different strategies for the development of effective vaccines and therapeutic combinations to deal with this viral outbreak. Overall, by the inclusion of various references, this review covers, in detail, the most important aspects of the COVID-19 pandemic.

Differential cytotoxicity of copper ferrite nanoparticles in different human cells.

Copper ferrite nanoparticles (NPs) have the potential to be applied in biomedical fields such as cell labeling and hyperthermia. However, there is a lack of information concerning the toxicity of copper ferrite NPs. We explored the cytotoxic potential of copper ferrite NPs in human lung (A549) and liver (HepG2) cells. Copper ferrite NPs were crystalline and almost spherically shaped with an average diameter of 35 nm. Copper ferrite NPs induced dose-dependent cytotoxicity in both types of cells, evident by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and neutral red uptake assays. However, we observed a quite different susceptibility in the two kinds of cells regarding toxicity of copper ferrite NPs. Particularly, A549 cells showed higher susceptibility against copper ferrite NP exposure than those of HepG2 cells. Loss of mitochondrial membrane potential due to copper ferrite NP exposure was observed. The mRNA level as well as activity of caspase-3 enzyme was higher in cells exposed to copper ferrite NPs. Cellular redox status was disturbed as indicated by induction of reactive oxygen species (oxidant) generation and depletion of the glutathione (antioxidant) level. Moreover, cytotoxicity induced by copper ferrite NPs was efficiently prevented by N-acetylcysteine treatment, which suggests that reactive oxygen species generation might be one of the possible mechanisms of cytotoxicity caused by copper ferrite NPs. To the best of our knowledge, this is the first report showing the cytotoxic potential of copper ferrite NPs in human cells. This study warrants further investigation to explore the mechanisms of differential toxicity of copper ferrite NPs in different types of cells. Copyright © 2016 John Wiley & Sons, Ltd.

Genotoxicity of ferric oxide nanoparticles in Raphanus sativus: Deciphering the role of signaling factors, oxidative stress and cell death.

We have studied the genotoxic and apoptotic potential of ferric oxide nanoparticles (Fe2O3-NPs) in Raphanus sativus (radish). Fe2O3-NPs retarded the root length and seed germination in radish. Ultrathin sections of treated roots showed subcellular localization of Fe2O3-NPs, along with the appearance of damaged mitochondria and excessive vacuolization. Flow cytometric analysis of Fe2O3-NPs (1.0mg/mL) treated groups exhibited 219.5%, 161%, 120.4% and 161.4% increase in intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), nitric oxide (NO) and Ca(2+) influx in radish protoplasts. A concentration dependent increase in the antioxidative enzymes glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (LPO) has been recorded. Comet assay showed a concentration dependent increase in deoxyribonucleic acid (DNA) strand breaks in Fe2O3-NPs treated groups. Cell cycle analysis revealed 88.4% of cells in sub-G1 apoptotic phase, suggesting cell death in Fe2O3-NPs (2.0mg/mL) treated group. Taking together, the genotoxicity induced by Fe2O3-NPs highlights the importance of environmental risk associated with improper disposal of nanoparticles (NPs) and radish can serve as a good indicator for measuring the phytotoxicity of NPs grown in NP-polluted environment.

Comparative cytotoxicity of dolomite nanoparticles in human larynx HEp2 and liver HepG2 cells.

Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration-dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration-dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real-time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up-regulated whereas the anti-apoptotic gene bcl-2 was down-regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase-3 and caspase-9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N-acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level.

Anti-biofilm and antibacterial activities of zinc oxide nanoparticles against the oral opportunistic pathogens Rothia dentocariosa and Rothia mucilaginosa.

Species of the genus Rothia that inhabit the oral cavity have recently been implicated in a number of diseases. To minimize their role in oral infections, it is imperative to reduce and/or control the growth and biofilm formation activity of Rothia spp. In this study, two bacterial isolates, Ora-7 and Ora-16, were obtained from the oral cavity of a healthy male subject and identified as Rothia dentocariosa and Rothia mucilaginosa, respectively, using a polyphasic taxonomic approach. Antimicrobial and anti-biofilm formation activities of zinc oxide nanoparticles (ZnO-NPs), of average size 35 nm, were assessed in in vitro assays using Crystal Violet and live and dead staining techniques. The ZnO-NPs exhibited an IC50 value of 53 and 76 µg ml(-1) against R. dentocariosa and R. mucilaginosa, respectively. Biofilm-formation assays, performed on the surfaces of polystyrene plates, artificial teeth, and dental prostheses, revealed the efficacy of ZnO-NPs as a potential antibacterial agent for controlling the growth of Rothia isolates in both planktonic form and biofilm.

Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.

The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe2O4-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 µg/ml of ZnFe2O4-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48h of ZnFe2O4-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT(2) Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p<0.01) population of ZnFe2O4-NPs (100 µg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe2O4-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe2O4-NPs induced cellular and genetic damage.

Chemical diversity in leaf and stem essential oils of Origanum vulgare L. and their effects on microbicidal activities.

Essential oils (EOs) from the stems and leaves of Origanum vulgare L. grown in Saudi Arabia and Jordan were analyzed by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionization detector (FID) techniques on two different columns (polar and nonpolar). A detailed phytochemical analysis led to the identification of 153 constituents of these essential oils. Both Saudi and Jordanian plants are classified by chemotypes rich in cymyl-compounds. However, the Saudi Origanum contains carvacrol as the major component and is, thus, characterized as a carvacrol chemotype, while the Jordanian Origanum contains thymol as the major component, and, thus, it is classified as a thymol chemotype. In addition, the antimicrobial activities of the studied EOs and their major components, including carvacrol and thymol, were evaluated against various Gram-positive and Gram-negative microorganisms. All the tested compounds exhibited significant antimicrobial activity against all the tested bacteria. Among them, thymol demonstrated superior activity against all the tested organisms, followed by carvacrol. Moreover, results on oil composition and oil yield of O. vulgare L. from different parts of the world is compared in detail with the present outcomes.

Bacterial isolates exhibiting multidrug resistance, hemolytic activity, and high 16S rRNA gene similarity with well-known pathogens found in camel milk samples of Riyadh region.

Customary consumption of unpasteurized milk by the population in the central Najed region of Saudi Arabia may pose a health risk. Therefore, 80 camel milk samples were collected aseptically from seven different stations of Riyadh region. The biochemical and microbiological properties of these milk samples were determined. Nutrient agar and brain heart infusion agar were used to determine mesophilic aerobic counts (MACs). The MAC in each mL of milk varied from 60 to 16 × 104  CFU/mL on nutrient agar. Based on the colony morphology, 176 colonies were collected from different samples, and these isolates were de-replicated into 80 unique isolates using rep-PCR analysis. Surprisingly, the 16S rRNA sequence analysis of these strains revealed that more than one-third of the collected milk samples contained strains that share maximum sequence similarities with well-known pathogens, such as Brucella, Bacillus anthracis, Listeria monocytogenes, and MRSA. Furthermore, many strains exhibit 16S rRNA gene similarity with opportunistic pathogens such as Citrobacter freundii and Kytococcus schroeteri. Many strains exhibit ß-hemolytic activity and resistant to six different antibiotics. Our study suggested that consumption of raw camel milk from this region constitutes a great health risk.

Assessing Methanogenic Archaeal Community in Full Scale Anaerobic Sludge Digester Systems in Dubai, United Arab Emirates.

INTRODUCTION: Anaerobic digestion for methane production comprises of an exceptionally diverse microbial consortium, a profound understanding about which is still constrained. In this study, the methanogenic archaeal communities in three full-scale anaerobic digesters of a Municipal Wastewater Treatment Plant were analyzed by Fluorescence in situ hybridization and quantitative real-time Polymerase Chain Reaction (qPCR) technique. METHODS & MATERIALS: Fluorescence in situ hybridization (FISH) was performed to detect and quantify the methanogenic Archaea in the sludge samples whereas qPCR was carried out to support the FISH analysis. Multiple probes targeting domain archaea, different orders and families of Archaea were used for the studies. RESULTS AND DISCUSSION: In general, the aceticlastic organisms (Methanosarcinaceae & Methanosaetaceae) were more abundant than the hydrogenotrophic organisms (Methanobacteriales, Methanomicrobiales, Methanobacteriaceae & Methanococcales). Both FISH and qPCR indicated that family Methanosaetaceae was the most abundant suggesting that aceticlastic methanogenesis is probably the dominant methane production pathway in these digesters. CONCLUSION: Future work involving high-throughput sequencing methods and correlating archaeal communities with the main operational parameters of anaerobic digesters will help to obtain a better understanding of the dynamics of the methanogenic archaeal community in wastewater treatment plants in United Arab Emirates (UAE) which in turn would lead to improved performance of anaerobic sludge digesters.

Synthesis and characterization of some abundant nanoparticles, their antimicrobial and enzyme inhibition activity.

Although the antimicrobial activity of the engineered nanoparticles (NPs) is well known, the biochemical mechanisms underlying this activity are not clearly understood. Therefore, four NPs with the highest global production, namely SiO2, TiO2, ZnO, and Ag, were synthesized and characterized. The synthesized SiO2, TiO2, ZnO, and Ag NPs exhibit an average size of 11.12, 13.4, 35, and 50 nm, respectively. The antimicrobial activity of the synthesized NPs against bacteria and fungi were also determined. NPs-mediated inhibition of two very important enzymes, namely urease and DNA polymerase, is also reported. The synthesized NPs especially Ag and ZnO show significant antimicrobial activity against bacteria and fungi including methicillin-resistant Staphylococcus aureus even at low concentration. The DNA polymerase activity was inhibited at a very low concentration range of 2-4 µg/ml, whereas the urease activity was inhibited at a high concentration range of 50-100 µg/ml. Based on their ability to inhibit the urease and DNA polymerase, NPs can be arranged in the following order: Ag > ZnO > SiO2 > TiO2 and Ag > SiO2 > ZnO > TiO2, respectively. As the synthesized NPs inhibit bacterial growth and suppress the activity of urease and DNA polymerase, the use of these NPs to control pathogens is proposed.

Molybdenum nanoparticles-induced cytotoxicity, oxidative stress, G2/M arrest, and DNA damage in mouse skin fibroblast cells (L929).

The present investigation was aimed to study the cytotoxicity, oxidative stress, and genotoxicity induced by molybdenum nanoparticles (Mo-NPs) in mouse skin fibroblast cells (L929). Cells were exposed to different concentrations (1-100 µg/ml) of Mo-NPs (size 40 nm) for 24 and 48 h. After the exposure, different cytotoxicity assays (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide, MTT; neutral red uptake, NRU; and cellular morphology) and oxidative stress markers (lipid peroxidation, LPO; glutathione, GSH; and catalase) were studied. Further, Mo-NPs-induced intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage were also studied. L929 cells treated with Mo-NPs showed a concentration- and time-dependent decrease in cell viability and a loss of the normal cell morphology. The percentage cell viability was recorded as 25%, 42%, and 58% by MTT assay and 24%, 46%, and 56% by NRU assay at 25, 50, and 100 µg/ml of Mo-NPs, respectively after 48 h exposure. Furthermore, the cells showed a significant induction of oxidative stress. This was confirmed by the increase in LPO and ROS generation, as well as the decrease in the GSH and catalase levels. The decrease in MMP also confirms the impaired mitochondrial membrane. The cell cycle analysis and comet assay data revealed that Mo-NPs induced G2/M arrest and DNA damage in a concentration-dependent manner. Our results demonstrated, for the first time, Mo-NPs induced cytotoxicity, oxidative stress and genotoxicity in L929 cells. Thus, data suggest the potential hazardous nature of Mo-NPs.