Novel splicing-site mutation in DCAF17 gene causing Woodhouse-Sakati syndrome in a large consanguineous family.

BACKGROUND: Woodhouse-Sakati syndrome is a rare autosomal recessive disease with endocrine and neuroectodermal aberrations with heterogeneous phenotypes and disease course. The most common phenotypes of the disease are progressive sensorineural hearing loss and alopecia, mild-to-moderate mental retardation and hypogonadism. The disease results from mutations in the DCAF17 gene. METHOD: Here, we reported a large consanguineous pedigree with multiple affected individuals with Woodhouse-Sakati syndrome phenotypes. Laboratory tests confirmed the endocrine perturbance in affected individuals. To find out the underlying genetic change, whole-exome sequencing was carried out. RESULT: Analysis of the exome data identified a splicing-site deletion NM_025000.3:c.1423-1_1425delGACA in DCAF17 gene. Sanger sequencing confirmed the co-segregation of the variant with the disease phenotypes in the family. CONCLUSION: The variant is predicted to cause aberrant splicing, i.e., exon skipping, resulting in the translation of a truncated functionless protein which results in appearance of typical phenotypic features and clinical laboratory findings of Woodhouse-Sakati syndrome in affected members of the family.

Characterization, Antiplasmodial and Cytotoxic Activities of Green Synthesized Iron Oxide Nanoparticles Using Nephrolepis exaltata Aqueous Extract.

The use of non-toxic synthesis of iron oxide nanoparticles (FeO NPs) by an aqueous plant extract has proven to be a viable and environmentally friendly method. Therefore, the present investigation is based on the FeO NPs synthesis by means of FeCl3·6H2O as a precursor, and the plant extract of Nephrolepis exaltata (N. exaltata) serves as a capping and reducing agent. Various techniques were used to examine the synthesized FeO NPs, such as UV-Visible Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray (EDX). The FT-IR studies were used to identify different photoactive biomolecules at 3285, 2928, 1415, 1170, and 600 cm-1 in the wavenumber range from 4000 to 400 cm-1, indicating the -OH, C-H, C-O, C-C, and M-O groups, respectively. The XRD examination exhibited crystallinity, and the average diameter of the particle was 16 nm. The spherical nature of synthesized FeO NPs was recognized by SEM images, while the elemental composition of nanoparticles was identified by an EDX spectrophotometer. The antiplasmodial activity of synthesized FeO NPs was investigated against Plasmodium parasites. The antiplasmodial property of FeO NPs was evaluated by means of parasite inhibitory concentration, which showed higher efficiency (62 ± 1.3 at 25 µg/mL) against Plasmodium parasite if compared to plant extracts and precursor. The cytotoxicity of FeO NPs was also assessed in human peripheral blood mononuclear cells (PBMCs) under in vitro conditions. The lack of toxic effects through FeO NPs keeps them more effective for use in pharmaceutical and medical applications.

Characterization and Evaluation of Antimicrobial Potential of Trigonella incise (Linn) Mediated Biosynthesized Silver Nanoparticles.

The goal of the research was to explore a new green method used to synthesize silver nanoparticles (Ag NPs) from an aqueous extract of Trigonella incise, which serves as a reducing and stabilizing agent. The obtained results showed an 85% yield of nanoparticles by using 2:5 (v/v) of 5% plant extract with a 0.5 M solution of AgNO3. Different techniques were used to characterize the synthesized Ag NPs, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and UV-visible spectroscopy. The UV-visible spectra of green synthesized silver nanoparticles showed maximum absorption at a wavelength of 440 nm. The FT-IR studies revealed the stretching oscillation frequency of synthesized silver nanoparticles in the absorption band near 860 cm-1. Similarly, the bending and stretching oscillation frequencies of the NH function group were assigned to the band in the 3226 cm-1 and 1647 cm-1 regions. The bending vibration of C-O at 1159 cm-1 confirmed the carbonyl functional group that was also assigned to the small intensity band in the range of 2361 cm-1. The X-ray diffraction analysis of Ag NPs revealed four distinct diffraction peaks at 2θ of 38°, 45°, 65° and 78°, corresponds to (111), (200), (220) and (311) of the face-centered cubic shape. The round shape morphology of Ag NPs with a mean diameter in the range 20-80 nm was analyzed via SEM images. Furthermore, the nanoparticles showed more significant antimicrobial activity against Salmonella typhi (S. typhi) and Staphylococcus aureus (S. aureus) with an inhibition zone of 21.5 mm and 20.5 mm at 6 µg/mL concentrations, respectively, once compared to the standard reference. At concentrations of 2 µg/mL and 4 µg/mL, all of the bacterial strains showed moderate activity, with inhibition zones ranging from 11 mm to 18.5 mm. Even at high concentrations of AgNPs, S. typhi showed maximum resistance. The best antifungal activity was observed by synthesized Ag NPs against Candida albicans (C. albicans) with 21 mm zone of inhibition, as compared to a standard drug which gives 22 mm of inhibition. Therefore, we conclude that the antibacterial and antifungal activities showed satisfactory results from the synthesized Ag NPs.

Comparative Study of Antimicrobial Activity of Silver, Gold, and Silver/Gold Bimetallic Nanoparticles Synthesized by Green Approach.

Nanotechnology is one of the most recent technologies. It is uncertain whether the production of small-size nanoparticles (NPs) can be achieved through a simple, straightforward, and medicinally active phytochemical route. The present study aimed to develop an easy and justifiable method for the synthesis of Ag, Au, and their Ag/Au bimetallic NPs (BNPs) by using Hippeastrum hybridum (HH) extract, and then to investigate the effects of Ag, Au, and their Ag/Au BNPs as antimicrobial and phytotoxic agents. Ag, Au, and their Ag/Au BNPs were characterized by UV-visible spectroscopy, FT-IR spectroscopy, XRD, EDX, and SEM analysis. XRD analysis conferring to the face of face-centered cubic crystal structure with an average size of 13.3, 10.72, and 8.34 nm of Ag, Au, and Ag/Au BNPs, respectively. SEM showed that Ag, Au, and Ag/Au BNPs had spherical morphologies, with calculated nano measurements of 40, 30, and 20 nm, respectively. The EDX analysis confirmed the composition of elemental Ag signal of the HH-AgNPs with 22.75%, Au signal of the HH-AuNPs with 48.08%, Ag signal with 12%, and Au signal with 38.26% of the Ag/Au BNPs. The Ag/Au BNPs showed an excellent antimicrobial efficacy against Gram-positive Staphylococcus aureus, Actinomycetes meriye, Bacillus cereus, Streptococcus pyogenes, Methicillin-resistant Staphylococcus aureus, Micrococcus luteus, Streptococcus pneumonia, and Gram-negative Klebsiella pneumonia, Escherichia coli, and Serratia marcescens bacterial strains, as well as against three fungal strains (Aspergillus niger, Aspergillus fumigatus, and Aspergillus flavus) compared to HH extract, HH-AgNPs, and HH-AuNPs. However, further investigations are recommended to be able to minimize potential risks of application.

Effect of Lipid-Based Multiple Micronutrients Supplementation in Underweight Primigravida Pre-Eclamptic Women on Maternal and Pregnancy Outcomes: Randomized Clinical Trial.

Background and Objectives: In pre-eclampsia, restricted blood supply due to the lack of trophoblastic cell invasion and spiral artery remodeling is responsible for adverse pregnancies and maternal outcomes, which is added to by maternal undernutrition. This study was designed to observe the effect of multiple nutritional micronutrient supplements on the pregnancy outcomes of underweight pre-eclamptic women. To investigate the effects of lipid-based multiple micr supplementations (LNS-PLW) on pregnancy and maternal outcomes in underweight primigravida pre-eclamptic women. Materials and Methods: A total of 60 pre-eclamptic, underweight primigravida women from the antenatal units of tertiary care hospitals in the Khyber Pakhtunkhwa Province, Pakistan, were randomly divided into two groups (Group 1 and Group 2). The participants of both groups were receiving routine treatment for pre-eclampsia: iron (60 mgs) and folic acid (400 ug) IFA daily. Group 2 was given an additional sachet of 75 gm LNS-PLW daily till delivery. The pregnancy outcomes of both groups were recorded. The clinical parameters, hemoglobin, platelet count, and proteinuria were measured at recruitment. Results: The percentage of live births in Group 2 was 93% compared to 92% in Group 1. There were more normal vaginal deliveries (NVDs) in Group 2 compared to Group 1 (Group 2, 78% NVD; group 1, 69% NVD). In Group 1, 4% of the participants developed eclampsia. The frequency of cesarean sections was 8/26 (31%) in Group 1 and 6/28 (22%) in Group 2. The number of intrauterine deaths (IUDs) was only 1/28 (4%) in Group 2, while it was 2/26 (8%) in Group 1. The gestational age at delivery significantly improved with LNS-PLW supplementation (Group 2, 38.64 ± 0.78 weeks; Group 1, 36.88 ± 1.55 weeks, p-value 0.006). The Apgar score (Group 2, 9.3; Group 1, 8.4) and the birth weight of the babies improved with maternal supplementation with LNS-PLW (Group 2, 38.64 ± 0.78 weeks: Group 1, 36.88 ± 1.55; p-value 0.003). There was no significant difference in systolic blood pressure, while diastolic blood pressure (Group 2, 89.57 ± 2.08 mmHg; Group 1, 92.17 ± 5.18 mmHg, p-value 0.025) showed significant improvement with LNS-PLW supplementation. The hemoglobin concentration increased with the LNS-PLW supplement consumed in Group 2 (Group 2, 12.15 ± 0.78 g/dL; Group 1, 11.39 ± 0.48 g/dL, p-value < 0.001). However, no significant difference among the platelet counts of the two groups was observed. Conclusions: The pregnancy and maternal outcomes of underweight pre-eclamptic women can be improved by the prenatal daily supplementation of LNS-PLW during pregnancy, along with IFA and regular antenatal care and follow-up.

Phyto-Extract-Mediated Synthesis of Silver Nanoparticles Using Aqueous Extract of Sanvitalia procumbens, and Characterization, Optimization and Photocatalytic Degradation of Azo Dyes Orange G and Direct Blue-15.

Green synthesis of silver nanoparticles (AgNPs) employing an aqueous plant extract has emerged as a viable eco-friendly method. The aim of the study was to synthesize AgNPs by using plant extract of Sanvitalia procumbens (creeping zinnia) in which the phytochemicals present in plant extract act as a stabilizing and reducing agent. For the stability of the synthesized AgNPs, different parameters like AgNO3 concentration, volume ratios of AgNO3, temperature, pH, and contact time were studied. Further, AgNPs were characterized by UV-visible spectroscopy, FT-IR (Fourier Transform Infrared Spectroscopy), XRD (X-ray Diffraction), SEM (Scanning Electron Microscopy), and EDX (Energy Dispersive X-ray Spectrometer) analysis. FT-IR analysis showed that the plant extract contained essential functional groups like O-H stretching of carboxylic acid, N-H stretching of secondary amides, and C-N stretching of aromatic amines, and C-O indicates the vibration of alcohol, ester, and carboxylic acid that facilitated in the green synthesis of AgNPs. The crystalline nature of synthesized AgNPs was confirmed by XRD, while the elemental composition of AgNPs was detected by energy dispersive X-ray analysis (EDX). SEM studies showed the mean particle diameter of silver nanoparticles. The synthesized AgNPs were used for photocatalytic degradation of Orange G and Direct blue-15 (OG and DB-15), which were analyzed by UV-visible spectroscopy. Maximum degradation percentage of OG and DB-15 azo dyes was observed, without any significant silver leaching, thereby signifying notable photocatalytic properties of AgNPs.

Incidence of Helminthic and Viral Coinfections in Malaria Patients in the Tertiary Care Hospital Setup.

Introduction: This study determines the incidence of common viral and helminth coinfections with malaria in the tertiary care hospital set up in southern Khyber Pakhtunkhwa, Pakistan. Materials and Methods: The multidimensional research included malaria patients admitted to different hospitals of district Kohat during January and December 2021. Stool samples and blood were assembled from the patients. Giemsa-stained microscopy-positive samples were processed by the immunochromatography technique (ICT) to identify Plasmodium species. Common viral infections such as viral hepatitis (A, B, and C), HIV, and dengue (DENV) were analyzed by ICT kits while SARS-CoV-2 was confirmed through real-time PCR. Furthermore, the intestinal helminths were identified using the Kato-Katz thick smear method. Results: Among 1278 patients, 548 were diagnosed with malaria, 412 (75.2%) were positive for P. vivax infection, 115 (21%) for P. falciparum, and 21 (3.8%) for mixed malaria infection (P. vivax/P. falciparum), with a higher incidence among males (65.2%) than females (34.8%). Coinfection with helminths was positive in 215 (39.3%) malaria patients. The most common infections were caused by the Ascaris lumbricoides species (42.6%) followed by Enterobius vermicularis (31.7%) and hookworm. A total of 24.6% of malaria-positive cases were also coinfected with different viruses with higher frequencies of confection for HAV (8.2%) and DENV (6.2%), respectively. The patients revealed higher incidence of coinfections with P. falciparum (57%) as compared with P. vivax (39.2%) and mixed infections (3.7%). Conclusion: This study demonstrated that the study population exhibited a significant incidence of coinfections with intestinal helminth and viral malaria.

Antimicrobial Resistance and Associated Risk Factors for Clostridium difficile in Patients Attending Tertiary Care Settings.

To determine the incidence of antimicrobial-resistant emerging pathogens, Clostridium difficile, and its associated risk factors in tertiary care setups of Pakistan. This cross-sectional prospective study was conducted from January 2019 to December 2020, to determine the prevalence and antimicrobial resistance patterns of C. difficile strains isolated from 450 stool specimens of patients suffering from diarrhea hospitalized in tertiary care hospitals in Peshawar, Pakistan. The stool samples of the patients were processed for culture and detection of toxin A and toxin B by enzyme-linked immunosorbent assay (ELISA) and tpi PCR. The drug sensitivity test was performed for antibiotics including ampicillin, cefixime, cefepime, amoxicillin, nalidixic acid, sulpha/TMP (SXT), chloramphenicol, metronidazole, vancomycin, ciprofloxacin, levofloxacin, and imipenem. Of 450 stool specimens, 108 (24%) were positive for C. difficile by stool culture, whereas 115 (25.5%) were only positive for C. difficile toxins based on ELISA and PCR (128 (28.6%). Of 108, 90.7% (n = 98) isolates were resistant to one antibiotic, and 90 (83.4%) were resistant to three or more antimicrobials. The highest resistance rates were found against penicillin (83.3%) followed by amoxicillin (70%), nalidixic acid (61%), and metronidazole (38%), and the lowest resistance was found against vancomycin (6.4%) and imipenem (3.7%). CDI was statistically significantly correlated with increased age, use of antibiotics, abdominal surgeries, use of proton pump inhibitors and H2a, and presence of comorbidities. The high frequency of C. difficile in Peshawar, Pakistan, indicates that CDI is an important nosocomial infection in different hospitals. The results will be helpful for clinicians to redesign control and therapeutic strategies in hospitals.

Characterization and Antibacterial Potential of Iron Oxide Nanoparticles in Eradicating Uropathogenic E. coli.

Proper management and control measurements are needed to stop the spread of highly pathogenic E. coli isolates that cause urinary tract infections (UTI) by developing new antibacterial agents to ensure the safety of public health. Therefore, the present investigations were used to achieve the synthesis of iron oxide nanoparticles (IONPs) via a simple coprecipitation method using ferric nitrates Fe (NO3)3 as the precursor and hydrazine solution as the precipitator and to explore the antibacterial activity against eradicating Uropathogenic Escherichia coli (E. coli). The synthesized IONPs were further studied using a UV-vis spectrophotometer, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopic (SEM) analysis. The maximum surface plasmon resonance peak was observed as absorption at 320 nm in a colloidal solution to validate the synthesis of IONPs. The FT-IR analysis was used to identify different photoactive functional groups that were responsible for the reduction of Fe (NO3)3 to IONPs. The crystalline nature of synthesized IONPs was revealed by XRD patterns with an average particle size ranging as 29 nm. The SEM image was employed to recognize the irregular morphology of synthesized nanoparticles. Moreover, significant antibacterial activity was observed at 1 mg/mL stock solution but after (125, 250, and 500 µg/mL) dilution, the synthesized IONPs showed moderate activity and became inactive at lower concentrations. The morphological and biochemical tests were used to confirm the presence of E. coli in the samples. Furthermore, the minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were carried out to determine the inhibitory concentrations for the isolated bacteria. The isolated E. coli were also subjected to antibiotic sensitivity testing that showed high resistance to antibiotics such as penicillin and amoxicillin. Thus, the findings of this study were to use IONPs against antibiotic resistance that has been developed in an inappropriate way.

Synthesis of Plant-Mediated Iron Oxide Nanoparticles and Optimization of Chemically Modified Activated Carbon Adsorbents for Removal of As, Pb, and Cd Ions from Wastewater.

This research study was designed with the aim to prepare plant extract-mediated iron oxide nanoparticles (IONPs) and different chemically modified carbon adsorbents from the Parthenium hysterophorus plant and then optimize the carbon adsorbents by evaluating their adsorption applications in wastewater for the selected metal ions like arsenic (As3+), lead (Pb2+), and cadmium (Cd2+). The Fourier transform infrared spectroscopy (FTIR) technique was used to highlight functional groups in plant-mediated IONPs and chemically modified carbon adsorbents. A scanning electron microscopy study was conducted to explain the surface morphology of the adsorbents. Energy-dispersive X-rays was used for elemental analysis and X-ray diffraction for particle size and crystallinity of the adsorbents. From the study, it was found that the best optimum conditions were pH = 5-6, initial concentration of adsorbate of 10 mg/L, dose of adsorbent of 0.01 g, contact time of 90-120 min of adsorbent and adsorbate, and temperature of 25 °C. At optimum conditions, the adsorption capacities of IONPs for arsenic (As) 144.7 mg/g, lead (Pb) 128.01 mg/g, and cadmium (Cd) ions 122.1 mg/g were recorded. The activated carbon at optimum conditions showed adsorption capacities of 46.35 mg/g for As, 121.95 mg/g for Pb, and 113.25 mg/g for Cd ion. At equilibrium, Langmuir, Freundlich Temkin, and Dubinin-Radushkevich isotherms were applied on the experimental adsorption data having the best R2 values (0.973-0.999) by the Langmuir isotherm. High-correlation coefficient R2 values (0.996-0.999) were obtained from the pseudo-second-order for all cases, showing that the adsorption process proceeds through pseudo second-order kinetics. The apparent adsorption energy E value was in the range of 0.24-2.36 kJ/mol. The adsorption capacity of regenerated IONPs for As gradually decreased from 144.8 to 45.67 mg/g, for lead 128.15 to 41.65 mg/g, and cadmium from 122.10 to 31.20 mg/g in 5 consecutive cycles. The study showed that the synthesized IONPs and acid-activated carbon adsorbent were successfully used to remove selected metal ions from wastewater.

Lipid-based Nutritional Supplement Impact on Energy Intake, Appetite, Glucose and Insulin Levels in Under-Weight Pregnant and Lactating Women with Preeclampsia.

OBJECTIVE: To investigate the response of nutritional supplement (LNS-PLW) on appetite score, energy intake, insulin and glucose levels in preeclamptic women. DESIGN & PARTICIPANTS: Sixty under-weight preeclamptic primigravida were divided into two groups randomly and provided LNS-PLW/Placebo in the fasted state. Blood samples were collected at fasting state, after 30mins of supplementation, "ad libitum buffet" breakfast and lunch for glucose and insulin levels. RESULTS: Total energy intake was higher significantly in the LNS-PLW group, although during breakfast it was significantly reduced. The insulin and glucose concentration was significantly increased after 30min of supplementation in the LNS-PLW group. CONCLUSION: Intake of the LNS-PLW by pre-eclamptic women had short-term suppression on subsequent meal but improved total energy intake during trial.

Multiple-Drug Resistant Shiga Toxin-Producing E. coli in Raw Milk of Dairy Bovine.

INTRODUCTION: Raw milk may contain pathogenic microorganisms harmful to humans, e.g., multidrug-resistant Escherichia coli non-O157:H7, which can cause severe colitis, hemolytic uremia, and meningitis in children. No studies are available on the prevalence of Shiga toxin-producing E. coli (STEC O157:H7) in sick or healthy dairy animals in the Khyber Pakhtunkhwa Province of Pakistan. AIM: This study aimed to isolate, characterize, and detect antibiotic resistance in STEC non-O157:H7 from unpasteurized milk of dairy bovines in this province. MATERIALS AND METHODS: We collected raw milk samples (n = 800) from dairy farms, street vendors, and milk shops from different parts of the Khyber Pakhtunkhwa Province. E. coli was isolated from these samples followed by latex agglutination tests for serotyping. The detection of STEC was conducted phenotypically and confirmed by the detection of virulence genes genotypically. An antibiogram of STEC isolates was performed against 12 antibiotics using the disc diffusion method. RESULTS: A total of 321 (40.12%) samples were found to be positive for E. coli in this study. These samples were processed for the presence of four virulence genes (Stx1, Stx2, ehxA, eae). Forty samples (5.0%) were STEC-positive. Of these, 38%, 25%, 19%, and 18% were positive for Stx1, Stx2, ehxA, and eae, respectively. Genotypically, we found that 1.37% of STEC isolates produced extended-spectrum beta-lactamase (ESBL) and contained the blaCTX M gene. Resistance to various antibiotics ranged from 18% to 77%. CONCLUSION: This study highlights the risk of virulent and multidrug-resistant STEC non-O157:H7 in raw milk and the need for proper quality surveillance and assurance plans to mitigate the potential public health threat.

Biallelic mutations in FLG, TGM1, and STS genes segregated with different types of ichthyoses in eight families of Pakistani origin.

BACKGROUND: Congenital ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non-syndromic forms of congenital ichthyosis are further grouped into common ichthyosis (ichthyosis vulgaris and X-linked ichthyosis), autosomal recessive congenital ichthyosis, and keratopathic ichthyosis. OBJECTIVE: To identify sequence variants involved in different forms of hereditary ichthyoses. METHODS: We studied eight families with different types of ichthyosis including four families with autosomal recessive congenital ichthyosis and four families with common ichthyosis. Whole exome sequencing and PCR based genotyping was carried out to find out the molecular basis of disease. RESULTS: In one family, a novel duplication sequence variant NM_002016.2:c.2767dupT; NP_002007.1:p.Ser923PhefsTer2 was identified in FLG gene; in four families a previously reported nonsense sequence variant NM_000359.3:c.232C>T; NP_002007.1:p.Arg78Ter was identified in TGM1 gene, while, in three families of X-linked recessive ichthyosis, the whole STS gene (NM_001320752.2; NP_001307681.2) regions were deleted. STUDY LIMITATION: Gene expression studies have not been performed that would have strengthened the findings of computational analysis. CONCLUSION: This study highlights the significance of the c.232C>T variant in the TGM1 gene as a possible founder mutation, complete STS gene deletion as reported previously in Pakistani population, while novel sequence variant in the FLG gene expands the spectrum of variations in this gene. These findings may be used for genetic counseling of the studied families.

Revolutionizing Nanotechnology with Filago desertorum Extracts: Biogenic Synthesis of Silver Nanoparticles Exhibiting Potent Antioxidant and Antibacterial Activities.

In this study, we described the environmentally friendly biosynthesis of silver nanoparticles (AgNPs) utilizing ethanolic extract of Filago desertorum (F. desertorum) as a capping and reducing agent. We also looked at the antioxidant and antibacterial capacities of AgNPs. In order to determine the size, shape, and crystallinity of the created AgNPs, the current project was designed to produce AgNPs utilizing the crude extract of the F. desertorum. The effectiveness of the project was evaluated by UV-visible spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. AgNPs are monodispersed and spherical and have 50 nm average particle diameters, as determined using Image J software calculations and SEM observation. Four significant peaks from an XRD study, located at 38.46, 44.63, 64.81, and 77.74 nm, were used to calculate the average crystalline size of AgNPs which was reported to be 15 nm. In the crude extract of F. desertorum, it is possible to see the functional group peaks of a number of substances that are essential for bioreduction and the stability of the AgNPs. Antibacterial and antioxidant properties of AgNPs in vitro (DPPH, ABTS, H2O2, phosphomolybdenum, and ferric reducing power) were examined using conventional methods. The AgNPs showed maximum DPPH (72.51% with IC50 = 144.61 µg/mL), ABTS (75.24% with IC50 = 131.21 µg/mL), hydrogen peroxide (73.33% with IC50 = 115.05 µg/mL), phosphomolybdenum activity (73.43% with IC50 = 75.25 µg/mL), and observing reducing power (0.25) at a concentration of 250 g/mL. Inhibition by the AgNPs against the bacterial strain Staphylococcus aureus was greatest (12 mm). According to the current findings, AgNPs produced by F. desertorum have the highest potential for free radical scavenging and antibacterial activity, which can result in antioxidant and antibiotic agents.

6-Aminoflavone Activates Nrf2 to Inhibit the Phospho-JNK/TNF-α Signaling Pathway to Reduce Amyloid Burden in an Aging Mouse Model.

In the current study, we examined the antioxidant activity and anti-amyloidogenic potential of 6-aminoflavone in an adult mice model of d-galactose-induced aging. Male albino eight-week-old mice were assigned into four groups: 1. the control group (saline-treated), 2. d-galactose-treated mice (100 mg/kg/day, intravenously) for eight weeks, 3. d-galactose-treated mice (100 mg/kg/day, intravenously for eight weeks) and 6-AF-treated mice (30 mg/kg/day, intravenously for the final four weeks), and 4. 6-AF-treated mice (30 mg/kg/day i.p. for four weeks). We conducted many assays for antioxidant enzymes, including lipid peroxidation, catalase, glutathione (GSH), peroxidase (POD), and sulfoxide dismutase (SOD) (LPO). Western blotting was used to assess protein expression while the Morris water maze (MWM) and Y-maze (YM) were used to study behavior. The findings show that 6-AF greatly improved neuronal synapse and memory impairment brought on by d-galactose and it significantly inhibited BACE1 to reduce the amyloidogenic pathway of A (both amyloid ß production and aggregation) by upregulating Nrf2 proteins (validated through molecular docking studies) and suppressing phosphorylated JNK and TNF-α proteins in adult albino mice's brain homogenates. These findings suggest that 6-AF, through the Nrf2/p-JNK/TNF-α signaling pathway, can diminish the oxidative stress caused by d-galactose, as well as the amyloidogenic route of A formation and memory impairment.

Biological Control of Hyalomma Ticks in Cattle by Fungal Isolates.

Ticks pose a major threat to cattle health and production in Pakistan because they transmit pathogens of diseases like Babesiosis and Theileriosis. Hyalomma spp., found across Africa, Asia, and Europe, are especially problematic. This study explored biocontrol of Hyalomma spp. using spore-free fungal culture filtrates collected from dairy farm soil in Kohat, Pakistan. Three fungal species of the genera Alternaria, Aspergillus, and Penicillium were isolated, and their filtrates were tested against tick adults and larvae. Filtrate concentrations were prepared at different strengths. Data were taken after the exposure of adults and larvae ticks to various concentrations of the fungal filtrates. Results indicated that at 100% concentration, all fungal filtrates induced 100% mortality in adults and larvae. Decreasing filtrate concentration lowered tick mortality. The lowest concentration caused the least mortality. The effect was time- and dose-dependent. In conclusion, spore-free fungal culture filtrates can provide biocontrol of Hyalomma spp. in a time- and concentration-dependent manner. Further research should explore the active compounds causing mortality and optimal application methods. The process outlined here provides a natural biocontrol alternative to chemical pesticides to reduce tick infestations and associated cattle diseases in Pakistan.

Whole Exome Sequence Analysis for Inborn Errors of IL-12/IFN-γ Axis in Patient with Recurrent Typhoid Fever.

Background: The IL-12/IFN-γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi. Objective: The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN-γ axis in patients with recurrent typhoid fever. Methods: WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN-γ axis pathway. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor. Results: Out of 25 possible variations in the IL-12/IFN-γ axis genes, only 2 probable disease-causing mutations were identified. These variations were rare and include mutations in IL23R and ZNFX I. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors. Conclusion: Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN-γ axis. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN-γ axis genes with recurrent typhoid fever.

Phytosynthesized Iron Oxide Nanoparticles Using Aqueous Extract of Saccharum arundinaceum (Hardy Sugar Cane), Their Characterizations, Antiglycation, and Cytotoxic Activities.

The goal of the current study is to achieve plant-mediated synthesis of iron oxide nanoparticles (Fe2O3 NPs). The plant extract of Saccharum arundinaceum was used as a reducing and stabilizing agent for the synthesis of Fe2O3 NPs. Different techniques such as energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy (UV-vis) were used to characterize the synthesis of Fe2O3 NPs. UV-visible spectroscopy verified the synthesis of Fe2O3 NPs using a surface plasmon resonance peak at a wavelength of 370 nm. SEM analysis specifies the spherical morphology of the synthesized nanoparticles with a size range between 30 and 70 nm. The reducing and capping materials of Fe2O3 NPs were revealed by FT-IR analysis based on functional group identification. The plant extract contained essential functional groups, such as C-H, C-O, N-H, -CH2, and -OH, that facilitate the green synthesis of Fe2O3 NPs. The EDX analysis detected the atomic percentage with the elemental composition of Fe2O3 NPs, while the XRD pattern demonstrated the crystallinity of Fe2O3 NPs. Furthermore, the synthesized Fe2O3 NPs showed potential antiglycation activity under in vitro conditions, which was confirmed by the efficient zone of inhibition on glycation of bovine serum albumin/glucose (BSA-glucose) in the order <100 < 500 < 1000 µg/mL, which revealed that Fe2O3 NPs showed significant antiglycation activity. Additionally, the cytotoxic activity against brain glioblastoma cells was assessed using the MTT assay, which exhibited diminished cytotoxic activity at concentrations lower than 300 µg/mL. Thus, we assumed that the resulting Fe2O3 NPs are a good option for use in drug delivery and cancer treatments.

Biofabrication of Titanium Dioxide Nanoparticles Catalyzed by Solanum surattense: Characterization and Evaluation of their Antiepileptic and Cytotoxic Activities.

The green synthesis of nanoparticles using plant extract is a new method that can be used in various biomedical applications. Therefore, the green approach was an aspect of ongoing research for the synthesis titanium dioxide nanoparticles (TiO2 NP) using the Solanum surattense aqueous plant extract, which acts as a stabilizing and reducing agent. The synthesis of TiO2 NPs was confirmed by energy dispersive X-ray (EDX), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy (UV-vis) analyses. The excitation energy to synthesize TiO2 NPs was identified through the UV-vis spectrophotometric analysis at a wavelength of 244 nm. Further, the FT-IR spectroscopy visualized different biomolecules like OH, C=O, C-H, and C-O that were present in an aqueous extract of the plant and were responsible for the stabilization of TiO2 NPs. The crystallinity and phase purity of TiO2 NPs were illustrated by the sharp peaks of the XRD pattern. The spherical morphology with sizes ranging from 10 to 80 nm was examined using SEM images. The elemental composition of TiO2 NPs was revealed by the intensity and narrow widths of titanium and oxygen using EDX analysis. This report also explains the antiepileptic activity of TiO2 NPs in a maximal electroshock-induced epileptic (MESE) and pentylenetetrazol (PTZ) model. The synthesized TiO2 NPs showed maximum antiepileptic activity in the PTZ model, significantly decreasing the convulsions (65.0 ± 5.50 s) at 180 mg/kg in contrast to standard drug phenytoin, whereas the MESE model was characterized by the appearance of extensor, clonus, and flexion. The results showed that synthesized TiO2 NPs significantly reduced the time spent in each stage (15.3 ± 0.20, 16.8 ± 0.25, and 20.5 ± 0.14 s) at 180 mg/kg as compared to control groups. Furthermore, the cytotoxicity of synthesized produced TiO2 NPs demonstrated that concentrations ≤80 µg/mL were biologically compatible.

Antiplatelet, cytotoxic activities and characterization of green-synthesized zinc oxide nanoparticles using aqueous extract of Nephrolepis exaltata.

The goal of the current study was to synthesize zinc oxide nanoparticles (ZnO-NPs) using ZnCl2.2H2O salt precursor and an aqueous extract of Nephrolepis exaltata (N. exaltata), which act as a capping and reducing agent. N. exaltata plant extract-mediated ZnO-NPs were further characterized by various techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), UV-visible (UV-Vis), and energy-dispersive X-ray (EDX) analysis. The nanoscale crystalline phase of ZnO-NPs was analyzed by the XRD patterns. The FT-IR analysis revealed different functional groups of biomolecules involved in the reduction and stabilization of the ZnO-NPs. The light absorption and optical properties of ZnO-NPs were examined by UV-Vis spectroscopy at a wavelength of 380 nm. The spherical shape morphology of ZnO-NPs with mean particle size ranges between 60 and 80 nm was confirmed by SEM images. While the EDX analysis was used to identify the elemental composition of ZnO-NPs. Furthermore, the synthesized ZnO-NPs demonstrate potential antiplatelet activity by inhibiting the platelet aggregation induced by platelet activation factor (PAF) and arachidonic acid (AA). The results showed that synthesized ZnO-NPs were more effective in inhibiting platelet aggregation induced by AA with IC50 (56% and 10 µg/mL) and PAF (63% and 10 µg/mL), respectively. However, the biocompatibility of ZnO-NPs was assessed in human lung cancer cell line (A549) under in vitro conditions. The cytotoxicity of synthesized nanoparticles revealed that cell viability decreased and the IC50 was found to be 46.7% at a concentration of 75 µg/mL. The present work concluded the green synthesis of ZnO-NPs that was achieved by N. exaltata plant extract and showed good antiplatelet and cytotoxic activity, which demonstrates the lack of harmful effects making them more effective for use in pharmaceutical and medical fields to treat thrombotic disorders.