Sorafenib and Piperine co-loaded PLGA nanoparticles: Development, characterization, and anti-cancer activity against hepatocellular carcinoma cell line.

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for the treatment of advanced HCC; however, the reported response rate to such a therapeutic is suboptimal (<3%). Piperine (PIP) is an alkaloid demonstrated to exert a direct tumoricidal activity in HCC and improve the pharmacokinetic profiles of anticancer drugs including SORA. In this study, we developed a strategy to improve efficacy outcomes in HCC using PIP as an add-on treatment to support the first-line therapy SORA using biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). SORA and PIP (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) and stabilized with various concentrations of polyvinyl alcohol (PVA). The SORA and PIP-loaded PNPs (SP-PNPs) were characterized using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), and Scanning Electron Microscopy (SEM), Release of these drugs from SP-PNPs was investigated in vitro at both physiological and acidic pH, and kinetic models were employed to assess the mechanism of drug release. The in vitro efficacy of SP-PNPs against HCC cells (HepG2) was also evaluated. FTIR and XRD analyses revealed that the drugs encapsulated in PNPs were in an amorphous state, with no observed chemical interactions among the drugs or excipients. Assessment of drug release in vitro at pH 5 and 7.4 showed that SORA and PIP loaded in PNPs with 0.5 % PVA were released in a sustained manner, unlike pure drugs, which exhibited relatively fast release. SP-PNPs with 0.5 % PVA were spherical, had an average size of 224 nm, and had a high encapsulation efficiency (SORA âˆ¼ 82 %, PIP âˆ¼ 79 %), as well as superior cytotoxicity compared to SORA monotherapy in vitro. These results suggest that combining PIP with SORA using PNPs may be an effective strategy for the treatment of HCC and may set the stage for a comprehensive in vivo study to evaluate the efficacy and safety of this novel formulation using a murine HCC model.

Formulation of Silymarin-ß Cyclodextrin-TPGS Inclusion Complex: Physicochemical Characterization, Molecular Docking, and Cell Viability Assessment against Breast Cancer Cell Lines.

Silymarin (SIL) is a poorly water-soluble flavonoid reported for different pharmacological properties. Its therapeutic applications are limited due to poor water solubility. In this study, the solubility of silymarin has been enhanced by preparing freeze-dried binary and ternary complexes using beta cyclodextrin (ßCD) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS). The stoichiometry of the drug and the carrier was selected from the phase solubility study. The dissolution study was performed to assess the effect of complexation on the release pattern of SIL. The formation of inclusion complexes was confirmed by different physicochemical studies. Finally, a cell viability assay (MCF 7; breast cancer cell line) was performed to compare the activity with free SIL. The phase solubilization results revealed the formation of a stable complex (binary) with a stability constant and complexation efficiency (CE) value of 288 mol L-1 and 0.045%. The ternary sample depicted a significantly enhanced stability constant and CE value (890 mol L-1 and 0.14%). The release study results showed a marked increase in the release pattern after addition of ßCD (alone) in the binary mixture (49.4 ± 3.1%) as well as inclusion complex (66.2 ± 3.2%) compared to free SIL (32.7 ± 1.85%). Furthermore, with the addition of TPGS in SIL-ßCD (ternary), the SIL release was found to be significantly enhanced from the SIL ternary mixture (79.2 ± 2.13%) in 120 min. However, fast SIL release was achieved with 99.2 ± 1.7% in 45 min for the SIL ternary complex. IR and NMR spectral analysis results revealed the formation of a stable complex with no drug-polymer interaction. The formation of complexes was also confirmed by the molecular docking study (docking scores of 4.1 and -6.4 kcal/mol). The in vitro cell viability result showed a concentration-dependent activity. The IC50 value of the SIL ternary complex was found to be significantly lower than that of free SIL. The findings of the study concluded that the prepared SIL inclusion complex can be used as an alternative oral delivery system to enhance solubility, dissolution, and biological activity against the tested cancer cell line.

Preparation, optimization, and characterization of chrysin-loaded TPGS-b-PCL micelles and assessment of their cytotoxic potential in human liver cancer (Hep G2) cell lines.

In total, nine TPGS-b-PCL copolymers were synthesized employing distinct TPGS analogues (TPGS 2000, 3500, and 5000). In these copolymers, the length of the PCL chain varied according to the TPGS to PCL molecular weight ratio (1:1, 1:2, and 1:3). The formulation optimization was done by optimizing the drug to polymer ratio, encapsulation efficiency, drug loading, micelle diameter, and polydispersity index (PDI). TPGS3500-b-PCL7000 copolymer (TPGS to PCL ratio 1:2) with drug to polymer ratio 1:30 showed the best percentage encapsulation (63.50 ± 0.45 %) and drug loading (2.05 ± 0.07). The optimal micelle (CHR-M) diameter and PDI were determined to be 94.57 ± 13.40 nm and 0.16 ± 0.02, respectively. CHR-M showed slow release when compared with alcoholic solution of chrysin. Approximately 70.70 ± 6.4 % drug was released in 72 h. The CHR-M demonstrated considerably greater absorption in Hep G2 cells, which confirmed the reliability of the micellar carrier. The MTT assay results showed that the IC50 values for CHR-M were much lower after 24 and 48 h when compared to free chrysin. Therefore, CHR-M may be a viable carrier for active chrysin targeting with improved anticancer potential. Also, it could be a better alternative for the currently available treatment of hepatocellular carcinoma.

GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells.

The efficient delivery of small interfering RNA (siRNA) to the targeted cells significantly affects the regulation of the overexpressed proteins involved in the progression of several genetic diseases. SiRNA molecules in naked form suffer from low internalization across the cell membrane, high susceptibility to degradation by nuclease enzyme and low stability, which hinder their efficacy. Therefore, there is an urge to develop a delivery system that can protect siRNA from degradation and facilitate their uptake across the cell membrane. In this study, the cationic lipid (GL67) was exploited, in addition to DC-Chol and DOPE lipids, to design an efficient liposomal nanocarrier for siRNA delivery. The physiochemical characterizations demonstrated that the molar ratio of 3:1 has proper particle size measurements from 144 nm to 332 nm and zeta potential of -9 mV to 47 mV that depends on the ratio of the GL67 in the liposomal formulation. Gel retardation assay exhibited that increasing the percentage of GL67 in the formulations has a good impact on the encapsulation efficiency compared to DC-Chol. The optimal formulations of the 3:1 M ratio also showed high metabolic activity against A549 cells following a 24 h cell exposure. Flow cytometry findings showed that the highest GL67 lipid ratio (100 % GL67 and 0 % DC-Chol) had the highest percentage of cellular uptake. The lipoplex nanocarriers based on GL67 lipid could potentially influence treating genetic diseases owing to the high internalization efficiency and safety profile.

Effect of Apremilast on LPS-induced immunomodulation and inflammation via activation of Nrf2/HO-1 pathways in rat lungs.

Lipopolysaccharides (LPS), the lipid component of gram-negative bacterial cell wall, is recognized as the key factor in acute lung inflammation and is found to exhibit severe immunologic reactions. Phosphodiesterase-4 (PDE-4) inhibitor: "apremilast (AP)" is an immune suppressant and anti-inflammatory drug which introduced to treat psoriatic arthritis. The contemporary experiment designed to study the protective influences of AP against LPS induced lung injury in rodents. Twenty-four (24) male experimental Wistar rats selected, acclimatized, and administered with normal saline, LPS, or AP + LPS respectively from 1 to 4 groups. The lung tissues were evaluated for biochemical parameters (MPO), Enzyme Linked Immunosorbent Assay (ELISA), flowcytometry assay, gene expressions, proteins expression and histopathological examination. AP ameliorates the lung injuries by attenuating immunomodulation and inflammation. LPS exposure upregulated IL-6, TNF-α, and MPO while downregulating IL-4 which were restored in AP pretreated rats. The changes in immunomodulation markers by LPS were reduced by AP treatment. Furthermore, results from the qPCR analysis represented an upregulation in IL-1ß, MPO, TNF-α, and p38 whereas downregulated in IL-10 and p53 gene expressions in disease control animals while AP pretreated rats exhibited significant reversal in these expressions. Western blot analysis suggested an upregulation of MCP-1, and NOS-2, whereas HO-1, and Nrf-2 expression were suppressed in LPS exposed animals, while pretreatment with AP showed down regulation in the expression MCP-1, NOS-2, and upregulation of HO-1, and Nrf-2 expression of the mentioned intracellular proteins. Histological studies further affirmed the toxic influences of LPS on the pulmonary tissues. It is concluded that, LPS exposure causes pulmonary toxicities via up regulation of oxidative stress, inflammatory cytokines and stimulation of IL-1ß, MPO, TNF-α, p38, MCP-1, and NOS-2 while downregulation of IL-4, IL-10, p53, HO-1, and Nrf-2 at different expression level. Pretreatment with AP controlled the toxic influences of LPS by modulating these signaling pathways.

Assessment of the Anticancer Effect of Chlorojanerin Isolated from Centaurothamnus maximus on A549 Lung Cancer Cells.

The goal of this study was to assess the anticancer efficacy of chlorojanerin against various cancer cells. The effects of chlorojanerin on cell cytotoxicity, cell cycle arrest, and cell apoptosis were examined using MTT assay, propidium iodide staining, and FITC Annexin V assay. RT-PCR was employed to determine the expression levels of apoptosis-related genes. Furthermore, docking simulations were utilized to further elucidate the binding preferences of chlorojanerin with Bcl-2. According to MTT assay, chlorojanerin inhibited the proliferation of all tested cells in a dose-dependent manner with a promising effect against A549 lung cancer cells with an IC50 of 10 µM. Cell growth inhibition by chlorojanerin was linked with G2/M phase cell cycle arrest in A549 treated cells. Flow cytometry analysis indicated that the proliferation inhibition effect of chlorojanerin was associated with apoptosis induction in A549 cells. Remarkably, chlorojanerin altered the expression of many genes involved in apoptosis initiation. Moreover, we determined that chlorojanerin fit into the active site of Bcl-2 according to the molecular docking study. Collectively, our results demonstrate that chlorojanerin mediated an anticancer effect involving cell cycle arrest and apoptotic cell death and, therefore, could potentially serve as a therapeutic agent in lung cancer treatment.

Optimization of Gefitinib-Loaded Nanostructured Lipid Carrier as a Biomedical Tool in the Treatment of Metastatic Lung Cancer.

Gefitinib (GEF) is utilized in clinical settings for the treatment of metastatic lung cancer. However, premature drug release from nanoparticles in vivo increases the exposure of systemic organs to GEF. Herein, nanostructured lipid carriers (NLC) were utilized not only to avoid premature drug release but also due to their inherent lymphatic tropism. Therefore, the present study aimed to develop a GEF-NLC as a lymphatic drug delivery system with low drug release. Design of experiments was utilized to develop a stable GEF-NLC as a lymphatic drug delivery system for the treatment of metastatic lung cancer. The in vitro drug release of GEF from the prepared GEF-NLC formulations was studied to select the optimum formulation. MTT assay was utilized to study the cytotoxic activity of GEF-NLC compared to free GEF. The optimized GEF-NLC formulation showed favorable physicochemical properties: <300 nm PS, <0.2 PDI, <−20 ZP values with >90% entrapment efficiency. Interestingly, the prepared formulation was able to retain GEF with only ≈57% drug release within 24 h. Furthermore, GEF-NLC reduced the sudden exposure of cultured cells to GEF and produced the required cytotoxic effect after 48 and 72 h incubation time. Consequently, optimized formulation offers a promising approach to improve GEF's therapeutic outcomes with reduced systemic toxicity in treating metastatic lung cancer.

Chemical profile, antiproliferative and pro-apoptotic activities of essential oils of Pulicaria arabica against A549 lung cancer cell line.

Pulicaria arabica has been traditionally utilized in folk medicine for various purposes such as ulcer treatments as well as antidiarrheal agent. Herein, the chemical profiles of Pulicaria arabica essential oils (PAEOs) and the in vitro antiproliferative effect of PAEOs were investigated. Hydrodistillation was employed to prepare PAEOs which were then characterized by GC/MS, while the antiproliferative effects were investigated by MTT assay as well as flow cytometric and RT-PCR analysis. Sixty-four (99.99 %) constituents were recognized from PAEOs. Carvotanacetone (36.97 %), (-)-carvomenthone (27.20 %) and benzene, 2-(1,1-dimethylethyl)-1,4-dimethoxy- (6.92 %) were the main components. PAEOs displayed IC50 values ranging from 30 to 50 µg/mL. DNA content analysis revealed that A549 cells exposed to PAEOs exhibited an increase in G1 cells population. The flow cytometry analysis results also showed that the PAEOs antiproliferative effect was mediated via apoptosis induction. Furthermore, a modulation in the pro-apoptotic markers (caspase-3 and Bax) and anti-apoptotic (Bcl-2) was also observed. In conclusion, PAEOs exhibited a moderate anti-proliferative effect on A549 cells through modulating the cell cycle progression and apoptosis initiation. These findings could offer a potential therapeutic use of PAEOs in lung cancer treatment.

Formulation of Multicomponent Chrysin-Hydroxy Propyl ß Cyclodextrin-Poloxamer Inclusion Complex Using Spray Dry Method: Physicochemical Characterization to Cell Viability Assessment.

The work aimed to enhance chrysin (CHR) water solubility, dissolution, and in vitro antibacterial as well as cell viability. Chrysin binary, as well as ternary inclusion complex, were prepared using the spray drying method. The influence of an auxiliary component (poloxamer; PLX) was also assessed after being incorporated into the chrysin HP ßCD complex (CHR-BC) and formed as a chrysin ternary complex (CHR-TC). The phase solubility investigation was carried out in order to assess the complexation efficiency and stability constant. The samples were assessed for the dissolution test, physicochemical evaluation, antibacterial activity, and cell viability tests were also assessed. The results of the phase solubility investigation showed that the stability constant for the binary system (268 M-1) was lower than the ternary system (720 M-1). The complex stability was validated by the greater stability constant value. The dissolution results showed that pure CHR had a limited release of 32.55 ± 1.7% in 60 min, while prepared CHR-TC and CHR-BC both demonstrated maximum CHR releases of 99.03 ± 2.34% and 71.95 ±2.1%, respectively. The dissolution study's findings revealed that the release of CHR was much improved over that of pure CHR. A study using a scanning electron microscope showed that CHR-TC contains more agglomerated and amorphous components. The higher conversion of crystalline CHR into an amorphous form is responsible for the structural alterations that are observed. After complexation, the distinctive peaks of pure CHR changed due to the complexation with HP ßCD and PLX. The antimicrobial and cell viability results revealed improved antimicrobial activity as well as a lower IC50 value than pure CHR against the tested anticancer cell line (MCF7).

Formulation of Chitosan-Coated Apigenin Bilosomes: In Vitro Characterization, Antimicrobial and Cytotoxicity Assessment.

We prepared apigenin (APG)-loaded bilosomes (BLs) and evaluated them for vesicle size, zeta-potential and encapsulation efficiency. The formulations were prepared with cholesterol (CHL), sodium deoxy cholate (SDC), Tween 80 (T80) and phosphatidylcholine (PC) using solvent evaporation method. The prepared formulations showed the optimum result was coated with much mucoadhesive polymer chitosan (CH, 0.25 and 0.5% w/v). The chitosan-coated bilosomes (CH-BLs) were further evaluated for surface morphology, drug−polymer interaction, mucoadhesion, permeation, antimicrobial activity and cell viability. The prepared APG-BLs showed nano-metric size (211 ± 2.87 nm to 433 ± 1.98 nm), polydispersibility index <0.5, negative zeta potential (−15 to −29 mV) and enhanced encapsulation efficiency (69.5 ± 0.93 to 81.9 ± 1.3%). Based on these findings, selected formulation (F2) was further coated with chitosan and showed a marked increase in vesicle size (298 ± 3.56 nm), a positive zeta potential (+17 mV), superior encapsulation efficiency (88.1 ± 1.48%) and improved drug release (69.37 ± 1.34%). Formulation F2C1 showed significantly enhanced permeation and mucoadhesion (p < 0.05) compared to formulation F2 due to the presence of CH as a mucoadhesive polymer. The presence of CH on the surfaces of BLs helps to open the tight membrane junctions and leads to enhanced permeation. A TEM study revealed non-aggregated smooth surface vesicles. The antimicrobial and cell viability assessment revealed better effects in terms of zone of inhibition and cell line assessment against two different cancer cell line. From the study, it can be concluded that APG-CHBLs could be a superior alternative to conventional delivery systems.

Formulation and Evaluation of Luteolin-Loaded Nanovesicles: In Vitro Physicochemical Characterization and Viability Assessment.

Luteolin (LT) is a natural polyphenol water-insoluble compound. LT-loaded nanovesicles (NVs) were prepared by using the solvent evaporation method. LT-NVs were prepared using cholesterol, phosphatidylcholine, span 60, and labrasol in a different composition. The prepared LT-NVs were evaluated for encapsulation efficiency, in vitro drug release, and permeation study. The optimized LT-NVs were further evaluated for antioxidant activity and cytotoxicity using the lung cancer cell line. LT-NVs showed nanometric size (less than 300 nm), an optimum polydispersibility index (less than 0.5), and a negative zeta potential value. The formulations also showed significant variability in the encapsulation efficiency (69.44 ± 0.52 to 83.75 ± 0.35%) depending upon the formulation composition. The in vitro and permeation study results revealed enhanced drug release as well as permeation profile. The formulation LT-NVs (F2) showed the maximum drug release of 88.28 ± 1.13%, while pure LT showed only 20.1 ± 1.21% in 12 h. The release data revealed significant variation (p < 0.001) in the release pattern. The permeation results also depicted significant (p < 0.001) enhancement in the permeation across the membrane. The enhanced permeation from LT-NVs was achieved due to the enhanced solubility of LT in the presence of the surfactant. The antioxidant activity results proved that LT-NVs showed greater activity compared to pure LT. The cytotoxicity study showed lesser IC50 value from LT-NVs than the pure LT. Thus, it can be concluded that LT-NVs are a natural alternative to the synthetic drug in the treatment of lung cancer.

Janerin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis Involving the MAPK Pathway in THP-1, Leukemic Cell Line.

Janerin is a cytotoxic sesquiterpene lactone that has been isolated and characterized from different species of the Centaurea genus. In this study, janerin was isolated form Centaurothamnus maximus, and its cytotoxic molecular mechanism was studied in THP-1 human leukemic cells. Janerin inhibited the proliferation of THP-1 cells in a dose-dependent manner. Janerin caused the cell cycle arrest at the G2/M phase by decreasing the CDK1/Cyclin-B complex. Subsequently, we found that janerin promoted THP-1 cell death through apoptosis as indicated by flow cytometry. Moreover, apoptosis induction was confirmed by the upregulation of Bax, cleaved PARP-1, and cleaved caspase 3 and the downregulation of an anti-apoptotic Bcl-2 biomarker. In addition, immunoblotting indicated a dose dependent upregulation of P38-MAPK and ERK1/2 phosphorylation during janerin treatment. In conclusion, we have demonstrated for the first time that janerin may be capable of inducing cell cycle arrest and apoptosis through the MAPK pathway, which would be one of the mechanisms underlying its anticancer activity. As a result, janerin has the potential to be used as a therapeutic agent for leukemia.

Luteolin-Loaded Elastic Liposomes for Transdermal Delivery to Control Breast Cancer: In Vitro and Ex Vivo Evaluations.

The study aimed to prepare and optimize luteolin (LUT)-loaded transdermal elastic liposomes (LEL1-LEL12), followed by in vitro and ex vivo evaluations of their ability to control breast cancer. Various surfactants (Span 60, Span 80, and Brij 35), and phosphatidyl choline (PC) as a lipid, were used to tailor various formulation as dictated by "Design Expert® software (DOE). These were characterized for size, polydispersity index (PDI), and zeta potential. The optimized formulation (OLEL1) was selected for comparative investigations (in vitro and ex vivo) against lipo (conventional liposomes) and drug suspension (DS). Moreover, the in vitro anticancer activity of OLEL1 was compared against a control using MCF-7 cell lines. Preliminary selection of the suitable PC: surfactant ratio for formulations F1-F9 showed relative advantages of Span 80. DOE suggested two block factorial designs with four center points to identify the design space and significant factors. OLEL1 was the most robust with high functional desirability (0.95), minimum size (202 nm), relatively high drug release, increased drug entrapment (92%), and improved permeation rate (~3270 µg/cm2) as compared with liposomes (~1536 µg/cm2) over 24 h. OLEL1 exhibited a 6.2- to 2.9-fold increase in permeation rate as compared with DS (drug solution). The permeation flux values of OLEL1, and lipo were found to be 136.3, 64 and 24.3 µg/h/cm2, respectively. The drug disposition values were 670 µg, 473 µg and 148 µg, for OLEL1, lipo and DS, respectively. Thus, ex vivo parameters were significantly better for OLEL1 compared with lipo and DS which is attributed to the flexibility and deformability of the optimized formulation. Furthermore, OLEL1 was evaluated for anticancer activity and showed maximized inhibition as compared with DS. Thus, elastic liposomes may be a promising approach for improved transdermal delivery of luteolin, as well as enhancing its therapeutic efficacy in controlling breast cancer.

Toxicological interaction between tobacco smoke toxicants cadmium and nicotine: An in-vitro investigation.

Cigarettes and other tobacco products are used to obtain nicotine that is responsible for their stimulating effects. However, a lot of other organic and inorganic chemicals are also released along with nicotine. Cadmium (Cd) is one of the several heavy metals that are health hazards and is one of the inorganic elements released in tobacco smoke. The in-vitro investigation focused on exploring the effects of nicotine hydrogen tartrate (NHT) and cadmium (Cd) and their toxic interactions in the A549 cell line. In cell viability assay NHT exhibited its IC50 at 11.71 mM concentration, and the IC50 of Cd was found to be 83 µM after a 24 h exposure. Toxic effects of NHT (5 mM and 10 mM), Cd (50 µM and 100 µM), and their combination were also investigated by flowcytometry. The investigation included apoptotic and necrotic events, the effect on different cell cycle phases, and generation of reactive oxygen species by NHT, Cd, and their combination of different concentrations. Data reveal evident toxic effects of NHT, Cd, and NHT + Cd. It also indicates that the toxic interaction of NHT and Cd is not additive and appears to be minimal when compared with NHT or Cd exposures alone.

Anticancer Activity and Apoptosis Induction of Gold(III) Complexes Containing 2,2'-Bipyridine-3,3'-dicarboxylic Acid and Dithiocarbamates.

Three novel gold(III) complexes (1-3) of general composition [Au(Bipydc)(S2CNR2)]Cl2 (Bipydc = 2,2'-bipyridine-3,3'-dicarboxylic acid and R = methyl for dimethyldithiocarbamate (DMDTC), ethyl for diethyldithiocarbamate (DEDTC), and benzyl for dibenzyldithiocarbamate (DBDTC)) have been synthesized and characterized by elemental analysis, FTIR and NMR spectroscopic techniques. The spectral results confirmed the presence of both the Bipydc and dithiocarbamate ligands in the complexes. The in vitro cytotoxic studies demonstrated that compounds 1-3 were highly cytotoxic to A549, HeLa, MDA-231, and MCF-7 cancer cells with activities much higher (about 25-fold) than cisplatin. In order to know the possible mode of cell death complex 2, [Au(Bipydc)(DEDTC)]Cl2 was further tested for induction of apoptosis towards the MCF-7 cells. The results indicated that complex 2 induces cell death through apoptosis.

Fate of arsenic in living systems: Implications for sustainable and safe food chains.

Arsenic, a group 1 carcinogen for humans, is abundant as compared to other trace elements in the environment and is present mainly in the Earth's crust and soil. The arsenic distributions in different geographical regions are dependent on their geological histories. Anthropogenic activities also contribute significantly to arsenic release into the environment. Arsenic presents several complications to humans, animals, and plants. The physiology of plants and their growth and development are affected by arsenic. Arsenic is known to cause cancer and several types of organ toxicity, such as cardiotoxicity, nephrotoxicity, and hepatotoxicity. In the environment, arsenic exists in variable forms both as inorganic and organic species. From arsenic containing compartments, plants can absorb and accumulate arsenic. Crops grown on these contaminated soils pose several-fold higher toxicity to humans compared with drinking water if arsenic enters the food chain. Information regarding arsenic transfer at different trophic levels in food chains has not been summarized until now. The present review focuses on the food chain perspective of arsenic, which affects all components of the food chain during its course. The circumstances that facilitate arsenic accumulation in flora and fauna, as components of the food chain, are outlined in this review.

Enhanced Apoptosis by Functionalized Highly Reduced Graphene Oxide and Gold Nanocomposites in MCF-7 Breast Cancer Cells.

Graphene nanocomposites have gained significant interest in a variety of biological applications due to their unique properties. Herein, we have studied the apoptosis-inducing ability and anticancer properties of functionalized highly reduced graphene oxide (HRG) and gold nanoparticles (Au NPs)-based nanocomposites (AP-HRG-Au). Samples were prepared under facile conditions via simple stirring and ultrasonication. All the samples were tested for their anticancer properties against different human cancer cell lines including lung (A549), liver (HepG2), and breast (MCF-7) cancer cells using doxorubicin as a positive control. In order to enhance the solubility and bioavailability of the sample, HRG was functionalized with 1-aminopyrene (1-AP) as a stabilizing ligand. The ligand also facilitated the homogeneous growth of Au NPs on the surface of HRG by offering chemically specific binding sites. The synthesis of nanocomposites and the surface functionalization of HRG were confirmed by UV-Vis, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The structure and morphology of the as-prepared nanocomposites were established by high-resolution transmission electron microscopy. Because of the functionalization, the AP-HRG-Au nanocomposite exhibited enhanced physical stability and high dispersibility. A comparative anticancer study of pristine HRG, nonfunctionalized HRG-Au, and 1-AP-functionalized AP-HRG-Au nanocomposites revealed the enhanced apoptosis ability of functionalized nanocomposites compared to the nonfunctionalized sample, whereas the pristine HRG did not show any anticancer ability against all tested cell lines. Both HRG-Au and AP-HRG-Au have induced a concentration-dependent reduction in cell viability in all tested cell lines after 48 h of exposure, with a significantly higher response in MCF-7 cells compared to the remaining cells. Therefore, MCF-7 cells were selected to perform detailed investigations using apoptosis assay, cell cycle analysis, and reactive oxygen species measurements. These results suggest that AP-HRG-Au induces enhanced apoptosis in human breast cancer cells.

Formulation of Piperine-Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation.

The present research work is designed to prepare and evaluate piperine liposomes and piperine-chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (-7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.

The possible impact of socioeconomic, income, and educational status on adverse effects of drug and their therapeutic episodes in patients targeted with a combination of tuberculosis interventions.

First-line antituberculosis (anti-TB) compounds have been considered as proven components of the Directly Observed Treatment-Short course (DOTS). Drug therapy against tuberculosis has been categorized as I, II, or III following the Revised National Tuberculosis Control Program guidelines. Anti-TB are drugs are quite common and show limited adverse effects. However, first-line anti-TB compounds mediated DOTS therapy and were found with several complications. Thus, those drugs have been discontinued. Therefore, the present study was designed to find out the possible impact of socioeconomic, income, and educational status on the adverse effects of drugs and their therapeutic episodes in patients targeted with a combination of tuberculosis intervention. This study found that an increased incidence of tuberculosis was found in patients who have finished high school, contributing to a high percentage of adverse effects. Notably, adverse events were shown maximally in poor patients compared with rich- or high-income patients. On the contrary, a high prevalence of adverse events was shown to be increased in partially skilled workers compared with full-skilled workers. Consequently, adversely considerable events were implicated to be raised in patients associated with minimal socioeconomic class. Such interesting factors would help in monitoring such events in experimental patients.

Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage.

Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.