Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation.

Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 µg/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (-8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4'-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy.

PGPR Kosakonia Radicincitans KR-17 Increases the Salt Tolerance of Radish by Regulating Ion-Homeostasis, Photosynthetic Molecules, Redox Potential, and Stressor Metabolites.

Among abiotic stresses, salinity is a significant limiting factor affecting agricultural productivity, survival, and production, resulting in significant economic losses. Considering the salinity problem, the goal of this study was to identify a halotolerant beneficial soil bacterium to circumvent salinity-induced phytotoxicity. Here, strain KR-17 (having an irregular margin; a mucoid colony; Gm-ve short rod; optimum temperature, 30°C; pH 7.0; no any pigmentation; showed a positive response to citrate utilization, catalase, starch, sucrose, lactose, and dextrose, etc.) recovered from rhizosphere soils of the potato-cultivating field, tolerated surprisingly a high (18% NaCl; 3.-M concentration) level of salt and identified as Kosakonia radicincitans (Accession No. OM348535). This strain was discovered to be metabolically active, synthesized essential PGP bioactive molecules like indole-3-acetic acid (IAA), siderophore (iron-chelating compounds), ACC deaminase, and ammonia, the quantity of which, however, increased with increasing NaCl concentrations. Here, Raphanus sativus L. (radish) was taken as a model crop to evaluate the adverse impact of NaCl, as well as salinity alleviation by halotolerant K. radicincitans. Salinity-induced toxicity to R. sativus was increased in a dose-dependent way, as observed both in vitro and in vivo conditions. Maximum NaCl levels (15%) demonstrated more extreme harm and considerably reduced the plant's biological features. However, membrane damage, relative leaf water content (RLWC), stressor metabolites, and antioxidant enzymes were increased as NaCl concentration increased. In contrast, halotolerant K. radicincitans KR-17 relieved salinity stress and enhanced the overall performance of R. sativus (L.) by increasing germination efficiency, dry biomass, and leaf pigments even in salt-challenged conditions. Additionally, KR-17 inoculation significantly (p ≤ 0.05) improved plant mineral nutrients (Na, K, Ca, Mg, Zn, Fe, Cu, P, and N). Following inoculation, strain KR-17 enhanced the protein, carbohydrates, root pigments, amino acids (AsA and Lys), lipids, and root alkaloids in R. sativus (L.). Besides these, due to PGPR seed priming in NaCl-stressed/non-stressed conditions, membrane damage, RLWC, stressor metabolites, and antioxidant defense enzymes were dramatically reduced. The strong biofilm-forming capacity of K. radicincitans could result in both in vitro and in vivo colonization under NaCl stress. Conclusively, halotolerant K. radicincitans KR-17 may probably be investigated affordably as the greatest way to increase the production of radish under salinity-stressed soils.

Bacillus mojavensis, a Metal-Tolerant Plant Growth-Promoting Bacterium, Improves Growth, Photosynthetic Attributes, Gas Exchange Parameters, and Alkalo-Polyphenol Contents in Silver Nanoparticle (Ag-NP)-Treated Withania somnifera L. (Ashwagandha).

Discharge of nanoparticles (NPs) into aquatic and terrestrial ecosystems during manufacturing processes and from various commercial goods has become a significant ecotoxicological concern. After reaching soil systems, NPs cause deleterious effects on soil fertility, microbial activity, and crop productivity. Taking into consideration the medicinal importance of Withania somnifera (L.) (ashwagandha), the present study assessed the potential hazards of silver nanoparticles (Ag-NPs) and the toxicity amelioration by a metal-tolerant plant growth-promoting rhizobacterium (PGPR). Bacillus mojavensis BZ-13 (NCBI accession number MZ950923) recovered from metal-polluted rhizosphere soil, tolerated an exceptionally high level of Ag-NPs. The growth-regulating substances synthesized by B. mojavensis were increased with increasing concentrations (0-1000 µg mL-1) of Ag-NPs. Also, strain BZ-13 had the ability to form biofilm, produce alginate and exopolysaccharides (EPSs), as well maintain swimming and swarming motilities in the presence of Ag-NPs. Soil application of varying concentrations of Ag-NPs resulted in a dose-related reduction in growth and biochemical features of ashwagandha. In contrast, following soil inoculation, B. mojavensis relieved the Ag-NPs-induced phytotoxicity and improved plant productivity. Root, shoot length, dry biomass, and leaf area increased by 13, 17, 37, 25%, respectively, when B. mojavensis was applied with 25 mg/kg Ag-NPs when compared to noninoculated controls. Furthermore, the soil plant analysis development (SPAD) index, photosystem efficiency (Fv/Fm), PS II quantum yield (FPS II), photochemical quenching (qP), non-photochemical quenching (NpQ), and total chlorophyll and carotenoid content of BZ-13-inoculated plants in the presence of 25 mg Ag-NPs/kg increased by 33, 29, 41, 47, 35, 26, and 25%, respectively, when compared to noninoculated controls that were exposed to the same amounts of NPs. In addition, a significant (p ≤ 0.05) increase in 48, 18, 21, and 19% in withaferin-A (alkaloids), flavonoids, phenols, and tannin content, respectively, was recorded when plants were detached from bacterized and Ag-NP-treated plants. Leaf gas exchange parameters were also modulated in the case of inoculated plants. Furthermore, bacterial inoculation significantly decreased proline, lipid peroxidation, antioxidant enzymes, and Ag-NP's absorption and build-up in phyto-organs. In conclusion, soil inoculation with B. mojavensis may possibly be used as an alternative to protect W. somnifera plants in soil contaminated with nanoparticles. Therefore, phytohormone and other biomolecule-synthesizing and NP-tolerant PGPR strains like B. mojavensis might serve as an agronomically significant and cost-effective remediation agent for augmenting the yield and productivity of medicinally important plants like ashwagandha raised in soil contaminated with nanoparticles in general and Ag-NPs in particular.

Diclofenac removal from the wastewater using activated sludge and analysis of multidrug resistant bacteria from the sludge.

Diclofenac is an anti-inflammatory drug and has been frequently detected from the wastewater. In the present study, factors affecting diclofenac adsorption on sewage sludge was evaluated. At 1 mg/L initial diclofenac concentration, more than 80% diclofenac removal was achieved. Adsorption increased at higher concentration (100 mg/L concentration) and more than 99% diclofenac was adsorbed from the wastewater. Significant removal of diclofenac was observed after 5 min contact time. The adsorption efficacy was more than 98% after 50 and 60 min. Pseudo-first and second order kinetics revealed reasonable regression value (0.9) indicated that the model is best fitted. Diclofenac adsorption was extremely high at acidic pHs than alkaline range. The sludge samples showed the presence of multi drug resistant bacteria. Vancomycin-resistant enterococcus stains were 27%, Methicillin-resistant Staphylococcus aureus positive strains were 16.5% and Extended-spectrum betal-lactamase-harbouring Enterobacteriacea were 65.4% in the sludge. The drug resistance Enterobacteriaceae revealed 14 Klebsiella pneumonia strains, 11 strains from E. coli and two from the genus Enterobacter. To conclude, the activated sludge could be effectively utilized for the removal of diclofenac from wastewater.

Efficient photocatalytic degradation of industrial contaminants by Piper longum mediated ZnO nanoparticles.

Piper longum extract as a reducing agent in green synthesis method is used to synthesize ZnO nanoparticles (ZnO-NPs). The impact of the reductant on the structural, optical and surface morphological properties of ZnO-NPs can be analyzed. Piper longum extract has delicately tuned the band gap of ZnO-NPs. Increase in energy band gap indicates an increase in the number of capping molecules in the prepared ZnO nanoparticles. The carbohydrates and proteins not only play a fundamental role in ZnO capping, which is important for its stability, determination and biocompatibility. Thus obtained nanosized ZnO particles are confirmed by the surface morphological studies. Because of various surface interface properties might have different physical-chemical, desorption-adsorption abilities in the direction towards microbes, create different antibacterial performances. S.aureus has maximum inhibition zone of 23 mm and Escherichia coli has minimum inhibition zone of 7 mm. To assess the photocatalytic activity of the prepared ZnO-NPs under UV light irradiation, methyl orange, malachite green and methylene blue dyes were utilized as model contaminants. The degradation efficiency of MG, MB and MO dyes solution is found that 96%, 69% and 48% of degradation efficiency respectively under ultraviolet light irradiation. The properties of synthetic nanopowders suggest that they have important potential for a variety of biochemical and environmental applications.

Polyhydroxybutyrate degradation by biocatalyst of municipal sludge water and degradation efficacy in sequencing batch biofilm reactor.

The main aim of the study was to degrade poly-ß-hydroxybutyrate (P(3HB)) in the sequencing batch biofilm reactor (SBBR) using biocatalyst. Enrichment method was used for the isolation of P(3HB) degrading bacteria. These bacterial strains were isolated from the wastewater sludge sample treated with P(3HB) sheets. A total of 75 bacteria were isolated after 60 days of incubation. The zone of clearance varied between 12 ± 1 mm and 19 ± 2 mm. Two bacterial strains (Nitrobacter vulgaris SW1 and Pseudomonas aeruginosa KS10) showed rapid PHB degradation activity on agar plates. Plate screening experiments confirmed PHB degrading ability of P. aeruginosa KS10 and N. vulgaris SW1. Biodegrading potential improved after 72 h fermentation period. The bacteria produced depolymerase and enzyme activity was maximum after 72 h. The sequencing batch biofilm reactor (SBBR) co-cultured with N. vulgaris SW1 and P. aeruginosa KS10 was operated to remove PHB from the wastewater. Biofilm in the reactor degraded PHB and the production of polyhydroxybutyrate depolymerase influenced on PHB degradation. Polyhydroxybutyrate degradation improved continuously and maximum degradation (95.6%) was achieved after 8 days. The degradation of biopolymers help to reduce environmental pollution associated with the petroleum based polymers.

Gold and silver nanoparticles: Green synthesis, microbes, mechanism, factors, plant disease management and environmental risks.

Metal nanoparticles were being used in different processes of developmental sectors like agriculture, industry, medical and pharmaceuticals. Nano-biotechnology along with sustainable organic chemistry has immense potential to reproduce innovative and key components of the systems to support surrounding environment, human health, and industry sustainably. Different unconventional methods were being used in green chemistry to synthesize gold and silver nanoparticles from various microbes. So, we reviewed different biological processes for green synthesis of metal nanoparticles. We also studied the mechanism of the synthesis process and procedures to characterize them. Some metallic nanoparticles have shown their potential to act as antimicrobial agent against plant pathogens. Here, we outlined green nanoparticles synthesized from microbes and highlighted their role against plant disease management.

Nano-formulation of herbo-mineral alternative medicine from linga chenduram and evaluation of antiviral efficacy.

Traditional medicine is becoming a primary source of health care in many countries in recent years. The current study proposes a new dimension of understanding a traditional origin treatment, using herbo-mineral preparations in nanoform. The herbo-mineral preparation, Linga chenduram [HMLC], was prepared according to the ancient palm script protocol dates back to 1000 years. In search of alternative therapy for the coronavirus, an attempt was made to determine this ethnic medicine formulation's therapeutic potential for viral hepatitis infection. The Hepatitis C virus [HCV] has several genomic similarities with SARS-CoV-2 viruses. The herbo-mineral formulation (HMLC) were analyzed using UV-vis, EDAX, FTIR, XRD, SEM, and TEM studies. SEM images confirmed the ' presence of nanoparticles with agglomerated conditions having an average grain size of 18 to 25 nm. EDAX studies showed the presence of metallic components in oxide or sulfide form in HMLC. The HCV inhibitory effects of HMLC indicated a good response. The cytotoxicity of this preparation against the Huh-7 human hepatoma cell line was significant. The HMLC showed a strong inhibitory effect on HCV replication in a dose-dependent manner. The genomic component of HCV is similar to COVID -19 virus. The Hepatitis C virus (HCV) NS3/4A protease has a striking three-dimensional structural similarity to the SARS-CoV2 Mpro protease, particularly in the arrangement of key active site residues. So HMLC can be tried to treat coronavirus infection. At higher concentrations, HMLC exhibited over 100-fold inhibition. In the MTT assay, HMLC did not show any apparent cytotoxic effect on cell viability at the concentrations 1-100 µg. Histological studies indicated that the liver and kidney did not experience any toxicity by 7 and 15 consecutive days of administration of HMLC on experimental Wistar rats. Hence, the HMLC can be tried as a therapy for COVID -19 infections using the preparations strictly according to ethnopharmacological protocol and optimum doses.

Antimicrobial and cytotoxic activities of isoniazid connected menthone derivatives and their investigation of clinical pathogens causing infectious disease.

BACKGROUND: This work is development of new molecules of isoniazid derivatives as dealing with potential of antimicrobial activity against clinical pathogens causing infectious disease. Antimicrobial of novel Mannich base derivatives can be achieved via one-pot synthesis in green chemistry approach. This method offers efficient, mild reaction conditions and high yields. In this study, totally 12 compounds (1a-l) was prepared and screened for cytotoxic and antimicrobial activities. MATERIALS AND METHODS: Newly synthesised compounds were conformed via FT- IR, 1H, and 13C NMR (Nuclear Magnetic Resonance), and mass spectra analysis. All compounds were checked antibacterial activity against gram-positive bacteria of Enterococcus faecalis, Staphylococcus aureus and gram-negative bacteria of Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. All compounds were checked against antifungal activity against Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Aspergillus niger, and Microsporum audouinii. All compounds were screened for cytotoxic activity against the MCF-7 (Michigan Cancer Foundation-7) cancer cell line. RESULT: The compound 1g was highly (MIC: 0.25 µg/mL) active against gram-negative bacterial of P. aeruginosa, whereas other compounds 1e and 1h were more active (MIC: 2 µg/mL) in K. pneumoniae and also 1g (MIC: 2 µg/mL) was more active in E. faecalis than standard ciprofloxacin. Antifungal screening, the compound 1b was highly active (MIC: 0.25 µg/mL) against C. albicance,1g (MIC: 2 µg/mL) and 1h (MIC: 4 µg/mL) was significant of active against A. fumigatus, and the compound 1c (MIC: 4 µg/mL) was extremely active in M. audouinii than clotrimazole. Compound 1g (GI50 = 0.01 µM) exhibited high activity against the MCF-7 cell line, while 1b (GI50 = 0.02 µM) was equipotent active compared with standard doxorubicin. CONCLUSION: A novel set of isoniazid derivatives (1a-l) and 1h were synthesized and screened for antimicrobial and cytotoxic activities. We found some highly active molecules, which are evidencing to be a potential treatment of bacterial and fungal infection candidates.

Microbial influenced corrosion of processing industry by re-circulating waste water and its control measures - A review.

In this review article, illustrating the impact and fundamental stuff of microbially influenced corrosion (MIC) along with mechanism, maintenance of materials, human life, wellbeing and inhibitors for cooling towers. Corrosion is a natural mechanism of oxidation and reduction of metal ions by chemical and electrochemical processes and microorganism accumulation. MIC occurs through the aggregation of microbes which can be secreting the extra polymeric substances (EPS) that oxidation of the metal surface. According to the reviews, in the cooling water system, the corrosion begins in the anode charge because its oxidation reaction quickly takes place on the metal surface than the cathode charge. Annihilate the corrosion process needs certain helper substances such as chemical or green compounds, called inhibitors. Corrosion inhibitors typically adopt the adsorption mechanism due to the presence of organic hetero atoms. Chemical and green inhibitors are used to prevent corrosion processes and since ancient times, vast quantities of chemical inhibitors have been used in industry due to their effectiveness and consistency. But still, the chemical inhibitors are more toxic to humans and the environment. Instead of chemical inhibitors, green inhibitors (natural products like plant leaves, flowers, stem, buds, roots and sea algae) are developed and used in industries. Generally, green inhibitors contain natural compounds, high inhibition efficiency, economic, eco- and human-friendly, and strong potential features against corrosion. Thus, a lot of research is ongoing to discover the green inhibitors in various parts of plants and seaweeds.

Palmitoylation of Plasmodium alveolins promotes cytoskeletal function.

S-palmitoylation is a post-translational lipid modification that is widespread among Plasmodium proteins and essential for parasite development. Little is known about the contribution of palmitoylation to the function of individual parasite molecules and structures. Alveolins are major components of the subpellicular network (SPN), a cortical cytoskeleton primarily involved in providing mechanical strength to the cell. We show here that the alveolin IMC1c is palmitoylated on a conserved cysteine motif, and that non-palmitoylated IMC1c displays normal expression, stability and trafficking. However, mutant parasites exhibit reduced osmotic stress resistance and tensile strength. These findings support the hypothesis that alveolin palmitoylation enhances cytoskeletal function by strengthening the connection between the SPN and the adjoining inner membrane complex via lipid anchoring.

The Plasmodium alveolin IMC1a is stabilised by its terminal cysteine motifs and facilitates sporozoite morphogenesis and infectivity in a dose-dependent manner.

Apicomplexan parasites possess a unique cortical cytoskeleton structure composed of intermediate filaments. Its building blocks are provided by a conserved family of proteins named alveolins. The core alveolin structure is made up of tandem repeat sequences, thought to be responsible for the filamentous properties of these proteins. A subset of alveolins also possess conserved motifs composed of three closely spaced cysteine residues situated near the ends of the polypeptides. The roles of these cysteine motifs and their contribution to alveolin function remains poorly understood. The sporozoite-expressed IMC1a is unique within the Plasmodium alveolin family in having conserved cysteine motifs at both termini. Using transgenic Plasmodium berghei parasites, we show in this structure-function analysis that mutagenesis of the amino- or carboxy-terminal cysteine motif causes marked reductions in IMC1a protein levels in the parasite, which are accompanied by partial losses of sporozoite shape and infectivity. Our findings give new insight into alveolin function, identifying a dose-dependent effect of alveolin depletion on sporozoite size and infectivity, and vital roles of the terminal cysteine motifs in maintaining alveolin stability in the parasite.

Plasmodium alveolins possess distinct but structurally and functionally related multi-repeat domains.

The invasive and motile life stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle. The pellicle is characterised by a double-layered 'inner membrane complex' (IMC) located underneath the plasma membrane, which is supported by a cytoskeletal structure termed the subpellicular network (SPN). The SPN consists of intermediate filaments, whose major constituents include a family of proteins called alveolins. Here, we re-appraise the alveolins in the genus Plasmodium with respect to their repertoire, structure and interrelatedness. Amongst 13 family members identified, we distinguish two domain types that, albeit distinct at the primary structure level, are structurally related and contain tandem repeats with a consensus 12-amino acid periodicity. Analysis in Plasmodium berghei of the most divergent alveolin, PbIMC1d, reveals a zoite-specific expression in ookinetes and a subcellular localisation in the pellicle, consistent with its predicted role as a SPN component. Knockout of PbIMC1d gives rise to a wild-type phenotype with respect to ookinete morphogenesis, tensile strength, gliding motility and infectivity, presenting the first example of apparent functional redundancy amongst alveolin family members.

Distinct temporal recruitment of Plasmodium alveolins to the subpellicular network.

The zoite stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle, which is defined by a double membrane layer named the inner membrane complex (IMC). The IMC is supported by a cytoskeleton of intermediate filaments, termed the subpellicular network (SPN). Plasmodium IMC1 proteins, or alveolins, make up a conserved family of structurally related proteins that comprise building blocks of the SPN. Here, using green fluorescent protein (GFP) tagging in P. berghei, we show that the alveolins PbIMC1c and PbIMC1e are expressed in all three zoite stages. Our data reveal that PbIMC1e is assembled into the SPN concurrent with pellicle development, while PbIMC1c is assembled after pellicle formation. In the sexual stages, these processes are accompanied by different gene expressions from maternal and paternal alleles: PbIMC1e is expressed uniquely from the maternal allele, while PbIMC1c is expressed from the maternal allele in gametocytes, but from both parental alleles during ookinete development. These findings establish biogenesis of the cortical cytoskeleton in Plasmodium to be a complex and dynamic process, involving distinct parental gene expression and chronological recruitment of its protein constituents. While allelic replacement of the pbimc1c and pbimc1e genes with GFP-tagged versions was readily achieved using double crossover homologous recombination, attempts to disrupt these genes by this strategy only resulted in the integration of the selectable marker and GFP reporter into non-specific genomic locations. The recurrent inability to disrupt these genes provides the first genetic evidence that alveolins are necessary for asexual blood-stage parasite development in Plasmodium.

Extended-spectrum ß-lactamase-producing Klebsiella pneumoniae in the neonatal intensive care unit: does vancomycin play a role?

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Klebsiella species cause worldwide problems in neonatal intensive care units (NICUs). This study aimed to determine possible risk factors for infection or colonization with ESBL-producing Klebsiella pneumoniae (ESBLKp) during an outbreak in the NICU. METHODS: A retrospective cohort study was conducted among neonates admitted to the NICU of a teaching hospital in Riyadh, Saudi Arabia, during an outbreak of ESBLKp from April to July 2008. The incidence density ratio was calculated to determine possible predictors of ESBLKp colonization or infection. RESULTS: During 2,265 person-days of follow-up of 118 neonates, 4 became infected, and 8 were colonized with ESBLKp. Univariate analyzes revealed that, among 14 neonates who were treated with vancomycin, 9 (64.3%) developed infection or colonization with ESBLKp, whereas, among 104 neonates who were not treated with vancomycin, 3 (2.9%) were affected, with an incidence density ratio of 4.22 (95% confidence interval: 1.47-5.15). Parenteral feeding and mechanical ventilation were found to be marginally significant risk factors. CONCLUSION: Treatment with vancomycin appears to be a risk factor for infection or colonization with ESBLKp in the NICU setting.