Electrospun Cu-Co ferrite nanofibers: synthesis, structure, optical and magnetic properties, and anti-cancer activity.

In this study, we investigated Cu-Co ferrite nanofibers (NFs) that were synthesized for the first time employing the electrospinning technique. The structure, phase purity and crystallite size of all the prepared NFs were revealed by powder X-ray diffraction (PXRD) analysis. The NFs crystallized in the Fd3̄m (no. 227) space group and the cation distribution arrangement over distinct sites in their structure was analyzed. Scanning electron microscopy (SEM) together with energy-dispersive X-ray (EDX) spectroscopy analysis showed the microstructure of the NFs and verified their expected chemical compositions. High-resolution transmission electron microscopy (TEM) images confirmed the fibrous nature and the construction of the NFs. The band gap energies derived from the UV-vis reflectance spectra showed a blue shift with an increase in the amount of Cu in the sample from 1.42 eV to 1.86 eV. Magnetization (M) as a function of magnetic field (H) measurements performed at ambient and low temperatures showed the ferrimagnetic behavior of all the NFs. The magnetic parameters including coercivity (Hc), saturation magnetization (Ms), remanent magnetization (Mr), and squareness ratio were determined from the recorded magnetization curves. At 300 K, Ms was reduced from 78.8 to 42.4 emu g-1, Mr reduced from 22.8 to 7.6 emu g-1 and the Bohr magneton reduced from 3.3 to 1.8µB with an increase in the content of Cu in the samples. The same trend was observed at 10 K, where Ms was reduced from 93.7 to 50.9 emu g-1, Mr reduced from 60.9 to 35.9 emu g-1 and the Bohr magneton reduced from 3.94 to 2.16µB. Alternatively, Hc has the highest values for x = 0 (850 Oe at 300 K and 5220 Oe at 10 K) and x = 0.6 (800 Oe at 300 K and 5400 Oe at 10 K). The anti-cancer activity of the NFs was evaluated using the MTT cell viability assay, showing a reduction in the viability of both HCT-116 and HeLa cancer cells compared to non-cancerous HEK-293 cells after treatment with the NFs. Apoptotic activity was examined by DAPI staining, where treatment with the NFs induced chromatin condensation and nuclear disintegration in HCT-116 cells.

Progress and Perspectives in Colon Cancer Pathology, Diagnosis, and Treatments.

Worldwide, colon cancer is the third most frequent malignancy and the second most common cause of death. Although it can strike anybody at any age, colon cancer mostly affects the elderly. Small, non-cancerous cell clusters inside the colon, commonly known as polyps, are typically where colon cancer growth starts. But over time, if left untreated, these benign polyps may develop into malignant tissues and develop into colon cancer. For the diagnosis of colon cancer, with routine inspection of the colon region for polyps, several techniques, including colonoscopy and cancer scanning, are used. In the case identifying the polyps in the colon area, efforts are being taken to surgically remove the polyps as quickly as possible before they become malignant. If the polyps become malignant, then colon cancer treatment strategies, such as surgery, chemotherapy, targeted therapy, and immunotherapy, are applied to the patients. Despite the recent improvements in diagnosis and prognosis, the treatment of colorectal cancer (CRC) remains a challenging task. The objective of this review was to discuss how CRC is initiated, and its various developmental stages, pathophysiology, and risk factors, and also to explore the current state of colorectal cancer diagnosis and treatment, as well as recent advancements in the field, such as new screening methods and targeted therapies. We examined the limitations of current methods and discussed the ongoing need for research and development in this area. While this topic may be serious and complex, we hope to engage and inform our audience on this important issue.

Pr3+ Ion-Substituted Ni-Co Nano-Spinel Ferrites: Their Synthesis, Characterization, and Biocompatibility for Colorectal Cancer and Candidaemia.

Nanotherapeutics have attracted tremendous research interest in the modern pharmaceutical and biomedical industries due to their potential for drug development, targeted delivery, and therapeutic applications. Therefore, the current study underpins the synthesis of praseodymium ion (Pr3+)-substituted Ni0.5Co0.5Fe2O4 nano-spinel ferrites, (Co0.5Ni0.5PrxFe2-xO4 (0.0 ≤ x ≤ 0.10) NSFs, CoNiPr (x ≤ 0.10) NSFs) via the sonochemical route for its application as a nanotherapeutic treatment option. The synthesized nanomaterial was characterized using various analytical techniques, including scanning/transmission electron microscopy (SEM) and X-ray powder diffractometry (XRD). After substitution with Pr (x = 0.08), the particle size, polydispersity index, and zeta potential analysis indicated an increase in hydrodynamic diameter, with an average zeta potential value of -10.2 mV. The investigation of CoNiPr (x ≤ 0.10) NSFs on colorectal cancer (HCT-116) cells demonstrated a significant effect on cancer cell viability. The inhibitory concentration (IC50) of CoNiPr (x ≤ 0.10) NSFs was between 46 ± 0.91 and 288 ± 8.21 for HCT-116 cells. The effect of CoNiPr (x ≤ 0.10) NSFs on normal human embryonic kidney (HEK-293) cells showed a reduction in the HEK-293 cell viability; however, the cell viability was better than HCT-116. The NSFs treatment also showed morphological changes in cancer cell nuclei, as revealed by DAPI (4',6-diamidino-2-phenylindole), nuclear disintegration, and chromatic fragmentation, which are signs of apoptosis or programmed cell death. To examine the potential antifungal effects of CoNiPr NSFs on Candida albicans, known to cause candidemia among cancer patients, the viability of the cells was assessed post treatment with CoNiPr (x ≤ 0.10) NSFs. The increasing ratio of dopant had a moderate impact on the percentage of cell viability loss of 42, 44, and 43% with x = 0.06, 0.08, and 0.10, respectively. These results reinforce that increased dopant significantly impacts the antifungal properties of the synthesized nanomaterial. These findings support the idea that NSFs might be useful in pharmaceuticals.

Anticancer Activity of Au/CNT Nanocomposite Fabricated by Nanosecond Pulsed Laser Ablation Method on Colon and Cervical Cancer.

Gold nanoparticles (AuNPs) and carbon nanotubes (CNTs) are increasingly being investigated for cancer management due to their physicochemical properties, low toxicity, and biocompatibility. This study used an eco-friendly technique (laser synthesis) to fabricate AuNP and Au/CNT nanocomposites. AuNPs, Au/CNTs, and CNTs were tested as potential cancer nanotherapeutics on colorectal carcinoma cells (HCT-116) and cervical cancer cells (HeLa) using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In addition, the non-cancer embryonic kidney cells HEK-293 were taken as a control in the study. The cell viability assay demonstrated a significant reduction in cancer cell population post 48 h treatments of AuNPs, and Au/CNTs. The average cell viabilities of AuNPs, Au/CNTs, and CNTs for HCT-116 cells were 50.62%, 65.88%, 93.55%, and for HeLa cells, the cell viabilities were 50.88%, 66.51%, 91.73%. The cell viabilities for HEK-293 were 50.44%, 65.80%, 93.20%. Both AuNPs and Au/CNTs showed higher cell toxicity and cell death compared with CNT nanomaterials. The treatment of AuNPs and Au/CNTs showed strong inhibitory action on HCT-116 and HeLa cells. However, the treatment of CNTs did not significantly decrease HCT-116 and HeLa cells, and there was only a minor decrease. The treatment of AuNPs, and Au/CNTs, on normal HEK-293 cells also showed a significant decrease in cell viability, but the treatment of CNTs did not produce a significant decrease in the HEK-293 cells. This study shows that a simplified synthesis technique like laser synthesis for the preparation of high-purity nanomaterials has good efficacy for possible future cancer therapy with minimal toxicity.

Nano-sized warriors: zinc chromium vanadate nanoparticles as a dual solution for eradicating waterborne enterobacteriaceae and fighting cancer.

The revolution of biomedical applications has opened new avenues for nanotechnology. Zinc Chromium vanadate nanoparticles (VCrZnO4 NPs) have emerged as an up-and-coming candidate, with their exceptional physical and chemical properties setting them apart. In this study, a one-pot solvothermal method was employed to synthesize VCrZnO4 NPs, followed by a comprehensive structural and morphological analysis using a variety of techniques, including X-Ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, Energy-dispersive X-ray, and X-ray photoelectron spectroscopy. These techniques confirmed the crystallinity of the NPs. The VCrZnO4 NPs were tested for their antibacterial activity against primary contaminants such as Enterobacteriaceae, including Shigella flexneri, Salmonella cholerasis, and Escherichia coli, commonly found in hospital settings, using the broth dilution technique. The results indicated a stronger antibacterial activity of VCrZnO4 NPs against Shigella and Salmonella than E. coli. Electron microscopy showed that the NPs caused severe damage to the bacterial cell wall and membrane, leading to cell death. In addition, the study evaluated the anticancer activities of the metal complexes in vitro using colorectal cancer cells (HCT-116) and cervical cancer cells (HELA), along with non-cancer cells and human embryonic kidney cells (HEK-293). A vanadium complex demonstrated efficient anticancer effects with half-inhibitory concentrations (IC50) of 38.50+3.50 g/mL for HCT-116 cells and 42.25+4.15 g/mL for HELA cells. This study highlights the potential of Zinc Chromium vanadate nanoparticles as promising candidates for antibacterial and anticancer applications. Various advanced characterization techniques were used to analyze the properties of nanomaterials, which may help develop more effective and safer antibacterial and anticancer agents in the future.

Nanotechnology in Cancer Diagnosis and Treatment.

Traditional cancer diagnosis has been aided by the application of nanoparticles (NPs), which have made the process easier and faster. NPs possess exceptional properties such as a larger surface area, higher volume proportion, and better targeting capabilities. Additionally, their low toxic effect on healthy cells enhances their bioavailability and t-half by allowing them to functionally penetrate the fenestration of epithelium and tissues. These particles have attracted attention in multidisciplinary areas, making them the most promising materials in many biomedical applications, especially in the treatment and diagnosis of various diseases. Today, many drugs are presented or coated with nanoparticles for the direct targeting of tumors or diseased organs without harming normal tissues/cells. Many types of nanoparticles, such as metallic, magnetic, polymeric, metal oxide, quantum dots, graphene, fullerene, liposomes, carbon nanotubes, and dendrimers, have potential applications in cancer treatment and diagnosis. In many studies, nanoparticles have been reported to show intrinsic anticancer activity due to their antioxidant action and cause an inhibitory effect on the growth of tumors. Moreover, nanoparticles can facilitate the controlled release of drugs and increase drug release efficiency with fewer side effects. Nanomaterials such as microbubbles are used as molecular imaging agents for ultrasound imaging. This review discusses the various types of nanoparticles that are commonly used in cancer diagnosis and treatment.

Nanocarriers based novel and effective drug delivery system.

Nanotechnology has ultimately come into the domain of drug delivery. Nanosystems for delivery of drugs are promptly emerging science utilizing different nanoparticles as carriers. Biocompatible and stable nanocarriers are novel diagnosis tools or therapy agents for explicitly targeting locates with controllable way. Nanocarriers propose numerous advantages to treat diseases via site-specific as well as targeted delivery of particular therapeutics. In recent times, there are number of outstanding nanocarriers use to deliver bio-, chemo-, or immuno- therapeutic agents to obtain effectual therapeutic reactions and to minimalize unwanted adverse-effects. Nanoparticles possess remarkable potential for active drug delivery. Moreover, conjugation of drugs with nanocarriers protects drugs from metabolic or chemical modifications, through their way to targeted cells and hence increased their bioavailability. In this review, various systems integrated with different types of nanocarriers (inorganic. organic, quantum dots, and carbon nanotubes) having different compositions, physical and chemical properties have been discussed for drug delivery applications.

Modelling the impact of climate change on dengue outbreaks and future spatiotemporal shift in Pakistan.

Climate change has a significant impact on the intensity and spread of dengue outbreaks. The objective of this study is to assess the number of dengue transmission suitable days (DTSD) in Pakistan for the baseline (1976-2005) and future (2006-2035, 2041-2070, and 2071-2099) periods under Representative Concentration Pathway (RCP4.5 and RCP8.5) scenarios. Moreover, potential spatiotemporal shift and future hotspots of DTSD due to climate change were also identified. The analysis is based on fourteen CMIP5 models that have been downscaled and bias-corrected with quantile delta mapping technique, which addresses data stationarity constraints while preserving future climate signal. The results show a higher DTSD during the monsoon season in the baseline in the study area except for Sindh (SN) and South Punjab (SP). In future periods, there is a temporal shift (extension) towards pre- and post-monsoon. During the baseline period, the top ten hotspot cities with a higher frequency of DTSD are Karachi, Hyderabad, Sialkot, Jhelum, Lahore, Islamabad, Balakot, Peshawar, Kohat, and Faisalabad. However, as a result of climate change, there is an elevation-dependent shift in DTSD to high-altitude cities, e.g. in the 2020s, Kotli, Muzaffarabad, and Drosh; in the 2050s, Garhi Dopatta, Quetta, and Zhob; and in the 2080s, Chitral and Bunji. Karachi, Islamabad, and Balakot will remain highly vulnerable to dengue outbreaks for all the future periods of the twenty-first century. Our findings also indicate that DTSD would spread across Pakistan, particularly in areas where we have never seen dengue infections previously. The good news is that the DTSD in current hotspot cities is projected to decrease in the future due to climate change. There is also a temporal shift in the region during the post- and pre-monsoon season, which provides suitable breeding conditions for dengue mosquitos due to freshwater; therefore, local authorities need to take adaption and mitigation actions.

Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines: Effects of O-Methylation on Taxifolin and Quercetin as Preliminary Natural Leads.

Six flavonoids present in Pulicaria jaubertii, i.e., 7,3'-di-O-methyltaxifolin (1), 3'-O-methyltaxifolin (2), 7-O-methyltaxifolin (3), taxifolin (4), 3-O-methylquercetin (5), and quercetin (6), were tested for their anticancer activities. The methylated flavonoids, compounds 1-3 and 5, were evaluated for their anticancer activities in comparison to the non-methylated parent flavonoids taxifolin (4) and quercetin (6). The structures of the known compounds were reconfirmed by spectral analyses using 1H and 13C NMR data comparisons and HRMS spectrometry. The anticancer activity of these compounds was evaluated in colon cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT antiproliferative assays. The caspase-3 and caspase-9 expressions and DAPI (4', 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 µg/mL for compounds 1 to 6, respectively. All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6. The viability of the HEK-293 normal cells was found to be significantly higher than the viability of the cancerous cells at all of the tested concentrations, thus suggesting that all the compounds have better inhibitory activity on the cancer cell line. Apoptotic features such as chromatin condensation and nuclear shrinkage were also induced by the compounds. The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2.

In Vitro Antimicrobial and Anticancer Peculiarities of Ytterbium and Cerium Co-Doped Zinc Oxide Nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) are a promising platform for their use in biomedical research, especially given their anticancer and antimicrobial activities. This work presents the synthesis of ZnO NPs doped with different amounts of rare-earth ions of ytterbium (Yb) and cerium (Ce) and the assessment of their anticancer and antimicrobial activities. The structural investigations indicated a hexagonal wurtzite structure for all prepared NPs. The particle size was reduced by raising the amount of Ce and Yb in ZnO. The anticancer capabilities of the samples were examined by the cell viability MTT assay. Post 48-h treatment showed a reduction in the cancer cell viability, which was x = 0.00 (68%), x = 0.01 (58.70%), x = 0.03 (80.94%) and x = 0.05 (64.91%), respectively. We found that samples doped with x = 0.01 and x = 0.05 of Yb and Ce showed a better inhibitory effect on HCT-116 cancer cells than unadded ZnO (x = 0.00). The IC50 for HCT-116 cells of Ce and Yb co-doped ZnO nanoparticles was calculated and the IC50 values were x = 0.01 (3.50 µg/mL), x = 0.05 (8.25 µg/mL), x = 0.00 (11.75 µg/mL), and x = 0.03 (21.50 µg/mL). The treatment-doped ZnO NPs caused apoptotic cell death in the HCT-116 cells. The nanoparticles showed inhibitory action on both C. albicans and E. coli. It can be concluded that doping ZnO NPs with Yb and Ce improves their apoptotic effects on cancer and microbial cells.

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma.

Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

Synthesis of M-Ag3PO4, (M = Se, Ag, Ta) Nanoparticles and Their Antibacterial and Cytotoxicity Study.

Silver Phosphate, Ag3PO4, being a highly capable clinical molecule, an ultrasonic method was employed to synthesize the M-Ag3PO4, (M = Se, Ag, Ta) nanoparticles which were evaluated for antibacterial and cytotoxicity activities post-characterization. Escherichia coli and Staphylococcus aureus were used for antibacterial testing and the effects of sonication on bacterial growth with sub-MIC values of M-Ag3PO4 nanoparticles were examined. The effect of M-Ag3PO4 nanoparticles on human colorectal carcinoma cells (HCT-116) and human cervical carcinoma cells (HeLa cells) was examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and DAPI (4',6-diamidino-2-phenylindole) staining. Additionally, we analyzed the effect of nanoparticles on normal and non-cancerous human embryonic kidney cells (HEK-293). Ag-Ag3PO4 exhibited enhanced antibacterial activity followed by Ta-Ag3PO4, Ag3PO4, and Se-Ag3PO4 nanoparticles against E. coli. Whereas the order of antibacterial activity against Staphylococcus aureus was Ag3PO4 > Ag-Ag3PO4 > Ta-Ag3PO4 > Se-Ag3PO4, respectively. Percentage inhibition of E. coli was 98.27, 74.38, 100, and 94.2%, while percentage inhibition of S. aureus was 25.53, 80.28, 99.36, and 20.22% after treatment with Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4, respectively. The MTT assay shows a significant decline in the cell viability after treating with M-Ag3PO4 nanoparticles. The IC50 values for Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4 on HCT-116 were 39.44, 28.33, 60.24, 58.34 µg/mL; whereas for HeLa cells, they were 65.25, 61.27, 75.52, 72.82 µg/mL, respectively. M-Ag3PO4 nanoparticles did not inhibit HEK-293 cells. Apoptotic assay revealed that the numbers of DAPI stained cells were significantly lower in the M-Ag3PO4-treated cells versus control.

Therapeutic Intervention for Various Hospital Setting Strains of Biofilm Forming Candida auris with Multiple Drug Resistance Mutations Using Nanomaterial Ag-Silicalite-1 Zeolite.

Candida auris (C. auris), an emerging multidrug-resistant microorganism, with limited therapeutical options, is one of the leading causes of nosocomial infections. The current study includes 19 C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam, identified by 18S rRNA gene and ITS region sequencing. Drug-resistance-associated mutations in ERG11, TAC1B and FUR1 genes were screened to gain insight into the pattern of drug resistance. Molecular identification was successfully achieved using 18S rRNA gene and ITS region and 5 drug-resistance-associated missense variants identified in the ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains, grouped into 3 clades. The prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial was tested against the 3 clades of clinical C. auris strains. 4wt%Ag/TiZSM-5 prepared using conventional impregnation technique was used for comparative study, and nano formulations were characterized using different techniques. The antibiofilm activity of nanomaterials was tested by cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the clades of C. auris strains, 4 wt%Ag/TiZSM-5 and Ag-silicalite-1 demonstrated a significant (p = 1.1102 × 10-16) inhibitory effect on the biofilm's survival rate: the lowest inhibition value was (10%) with Ag-silicalite-1 at 24 and 48 h incubation. A profound change in morphogenesis in addition to the reduction in the number of C.auris cells was shown by SEM and light microscopy. The presence of a high surface area and the uniform dispersion of nanosized Ag species displays enhanced anti-Candida activity, and therefore it has great potential against the emerging multidrug-resistant C. auris.

Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells.

Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1ß, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be -370.426 Kcal/mol, while the supramolecular ternary complex alone was -38.732 Kcal/mol, with a potential energy difference of -331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.

Convenient Synthesis of N-Alkyl-2-(3-phenyl-quinoxalin-2-ylsulfanyl)acetamides and Methyl-2-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)acetylamino]alkanoates.

A series of 27 new quinoxaline derivatives (N-alkyl-[2-(3-phenyl-quinoxalin-2-ylsulfanyl)]acetamides, methyl-2-[2-(3-phenylquinoxalin-2-ylsulfanyl)-acetylamino]alkanoates, and their corresponding dipeptides) were prepared from 3-phenylquinoxaline-2(1H)-thione based on the chemoselective reaction with soft electrophiles. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to study the efficacy of 27 compounds on cancer cell viability and proliferation. A total of 13 compounds (4a-c, 5, 6, 8c, 9c, 9f, 10a, 10b, 11c, 12b, and 12c) showed inhibitory action on HCT-116 cancer cells and 15 compounds (4a-c, 5, 6, 8c, 9a, 9c, 9f, 9h, 10b, 11c, 12a, 12b, and 12c) showed activity on MCF-7 cancer cells, with compound 10b exhibiting the highest inhibitory action (IC50 1.52 and 2 µg/mL, respectively) on both cell lines. The molecular modeling studies on the human thymidylate synthase (hTS) homodimer interface showed that these compounds are good binders and could selectively inhibit the enzyme by stabilizing its inactive conformation. The study also identified key residues for homodimer binding, which could be used for further optimization and development.

Water availability and response of Tarbela Reservoir under the changing climate in the Upper Indus Basin, Pakistan.

Agriculture is one of the major contributors to the Gross Domestic Product (GDP) of Pakistan which relies on the availability of water. Hydropower contributes approximately 35% to the national electricity gid of Pakistan. Indus River is the main river of the Indus River System (IRS) which provides water for agriculture, hydropower and other purposes. The outputs of the Conformal-Cubic Atmospheric Model (CCAM) are used to force the University of British Columbia Watershed Model (UBCWM) in the Upper Indus Basin (UIB), to investigate future water availability under the two IPCC emission scenarios (RCP4.5 and RCP8.5). Tarbela Reservoir which is the outlet of UIB is used as a measurement tool to assess water availability and response of the reservoir to climate change. The results show that maximum and minimum temperature are increasing in the future in comparison to the reference period. The largest increases in maximum temperature are projected for MAM (March-April-May) and JJA (June-July-August), with increases up to 2 °C in MAM and increases up to 6.4 °C in JJA under the RCP4.5 and RCP8.5, respectively, in the future. Minimum temperature has maximum increase (6.7 °C) in DJF (December-January-February) during 2071-2100 under RCP8.5. Precipitation shows a 5.1% decrease in DJF during 2011-2040 under RCP4.5. The statistics about water availability suggest that there is consistent increase in most of the months in the future, however, under the RCP4.5, there is decline in the river flow during 2071-2100 as compared to the 2041-2070. The findings of this study show that most of the time there will be more water available but in some months, there may be water scarcity under the RCP4.5, however, proper management and optimal utilization can reduce the water scarcity.

Biocompatibility and colorectal anti-cancer activity study of nanosized BaTiO3 coated spinel ferrites.

In the present work, different nanoparticles spinel ferrite series (MFe2O4, Co0.5M0.5Fe2O4; M = Co, Mn, Ni, Mg, Cu, or Zn) have been obtained via sonochemical approach. Then, sol-gel method was employed to design core-shell magnetoelectric nanocomposites by coating these nanoparticles with BaTiO3 (BTO). The structure and morphology of the prepared samples were examined by X-ray powder diffraction (XRD), scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscope (HR-TEM), and zeta potential. XRD analysis showed the presence of spinel ferrite and BTO phases without any trace of a secondary phase. Both phases crystallized in the cubic structure. SEM micrographs illustrated an agglomeration of spherical grains with nonuniformly diphase orientation and different degrees of agglomeration. Moreover, HR-TEM revealed interplanar d-spacing planes that are in good agreement with those of the spinel ferrite phase and BTO phase. These techniques along with EDX analyses confirmed the successful formation of the desired nanocomposites. Zeta potential was also investigated. The biological influence of (MFe2O4, CoMFe) MNPs and core-shell (MFe2O4@BTO, CoMFe@BTO) magnetoelectric nanocomposites were examined by MTT and DAPI assays. Post 48 h of treatments, the anticancer activity of MNPs and MENCs was investigated on human colorectal carcinoma cells (HCT-116) against the cytocompatibility of normal non-cancerous cells (HEK-293). It was established that MNPs possess anti-colon cancer capability while MENCs exhibited a recovery effect due to the presence of a protective biocompatible BTO layer. RBCs hemolytic effect of NPs has ranged from non- to low-hemolytic effect. This effect that could be attributed to the surface charge from zeta potential, also the CoMnFe possesses the stable and lowest zeta potential in comparison with CoFe2O4 and MnFe2O4 also to the protective effect of shell. These findings open up wide prospects for biomedical applications of MNPs as anticancer and MENCs as promising drug nanocarriers.

Climate change and spatio-temporal trend analysis of climate extremes in the homogeneous climatic zones of Pakistan during 1962-2019.

Climate extremes, such as heat waves, droughts, extreme rainfall can lead to harvest failures, flooding and consequently threaten the food security worldwide. Improving our understanding about climate extremes can mitigate the worst impacts of climate change and extremes. The objective here is to investigate the changes in climate and climate extremes by considering two time slices (i.e., 1962-1990 and 1991-2019) in all climate zones of Pakistan by utilizing observed data from 54 meteorological stations. Different statistical methods and techniques were applied on observed station data to assess changes in temperature, precipitation and spatio-temporal trends of climatic extremes over Pakistan from 1962 to 2019. The Mann-Kendal test demonstrated increasing precipitation (DJF) and decreasing maximum and minimum temperatures (JJA) at the meteorological stations located in the Karakoram region during 1962-1990. The decadal analysis, on the other hand, showed a decrease in precipitation during 1991-2019 and an increase in temperature (maximum and minimum) during 2010-2019, which is consistent with the recently observed slight mass loss of glaciers related to the Karakoram Anomaly. These changes are highly significant at 5% level of significance at most of the stations. In case of temperature extremes, summer days (SU25) increased except in zone 4, TX10p (cold days) decreased across the country during 1962-1990, except for zones 1 and 2. TX90p (warm days) increased between 1991-2019, with the exception of zone 5, and decreased during 1962-1990, with the exception of zones 2 and 5. The spatio-temporal trend of consecutive dry days (CDD) indicated a rising tendency from 1991 to 2019, with the exception of zone 4, which showed a decreasing trend. PRCPTOT (annual total wet-day precipitation), R10 (number of heavy precipitation days), R20 (number of very heavy precipitation days), and R25mm (very heavy precipitation days) increased (decreased) considerably in the North Pakistan during 1962-1990 (1991-2019). The findings of this study can help to address some of the sustainable development goals related climate action, hunger and environment. In addition, the findings can help in developing sustainable adaptation and mitigation strategies against climate change and extremes. As the climate and extremes conditions are not the uniform in all climate zone, therefore, it is suggested to the formers and agriculture department to harvest crops resilient to the climatic condition of each zone. Temperature has increasing trend in the northern Pakistan, therefore, the concerned stakeholders need to make rational plans for higher river flow/flood situation due to snow and glacier melt.

Template-free preparation of iron oxide loaded hollow silica spheres and their anticancer proliferation capabilities.

Hollow silica spheres (HSS) exhibited high-specific surface area, low toxicity, low density, and good biocompatibility. The effectivity of HSS material can be improved further by loading nanoparticles for smart biological applications. In this work, magnetic nanoparticle (iron oxide; Fe3O4)-loaded pure HSS (c-HSS-Fe) were synthesized successfully using a template-free chemical route and investigated for their anticancer cell proliferation capabilities against cancerous cell lines: human colorectal carcinoma cells (HCT-116). The structure, morphology, chemical bonding, and thermal stability of the prepared HSS derivatives were studied using spectroscopic and microscopic techniques. Our analyses confirmed the successful preparation of Fe3O4 loaded HSS material (sphere diameter ∼515 nm). The elemental analysis revealed the existence of Fe along with Si and O in the Fe3O4 loaded HSS material, thus reaffirming the production of the c-HSS-Fe product. The effects of silica spheres on HCT-116 cells were examined microscopically and by MTT assays. It was observed that the c-HSS-Fe demonstrated dose-dependent behavior and significantly reduced the cancer cell proliferation at higher doses. Our results showed that c-HSS-Fe was more effective and profound in reducing the cancer cells' activities as compared to unloaded HSS material where the cancer cells have undergone nuclear disintegration and fragmentation. It is concluded that c-HSS-Fe is a powerful bio-active material against cancerous cells.

Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2'-(2-Oxo-1H-benzo[d]imidazole-1,3(2H)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives.

To identify new candidate anticancer compounds, we here report the synthesis of benzimidazole derivatives: diethyl 2,2'-(2-oxo-1H-benzo[d]imidazole-1,3(2H)-diyl) diacetate and its arylideneacetohydrazide derivatives, using ultrasonic irradiation and conventional heating. The compounds were confirmed by Nuclear magnetic resonance (NMR) (JEOL, Tokyo, Japan) and Fourier transform infrared spectroscopy (FTIR) spectroscopy (Thermoscientific, Waltham, MA, USA). The molecular structure and electronic properties of the studied compounds were predicted for the acetohydrazide hydrazones. These compounds exist as a mixture of configurational and conformational isomerism as well as amido-amidic acid tautomerism. The NMR spectral data proved the predominance of syn-E amido isomers. In addition, density functional theory (DFT) predicted stability in the gas phase and showed that syn-E amido isomers are the most stable in the presence of an electron donating group, while the anti-isomer is the most stable in the presence of electron-attracting substituents. The anticancer activity of these synthetic compounds 6a, 6b and 6c towards both colon cancer (HCT-116) and cervical cancer (HeLa) cells was examined by MTT assay and DAPI staining. The MTT assay revealed a strong antiproliferative effect against the cancer cells at low concentrations, and interestingly, no significant inhibitory action against the non-cancerous cell line, HEK-293. The IC50 values for HCT-116 were 29.5 + 4.53 µM, 57.9 + 7.01 µM and 40.6 + 5.42 µM for 6a, 6b, and 6c, respectively. The IC50 values for HeLa cells were 57.1 + 6.7 µM, 65.6 + 6.63 µM and 33.8 + 3.54 µM for 6a, 6b, and 6c, respectively. DAPI staining revealed that these synthesized benzimidazole derivatives caused apoptotic cell death in both the colon and cervical cancer cells. Thus, these synthetic compounds demonstrate encouraging anticancer activity as well as being safe for normal human cells, making them attractive candidates as anticancer agents.