Green synthesis of ginger-encapsulated zinc oxide nanoparticles: Unveiling their characterization and selective cytotoxicity on MDA-MB 231 breast cancer cells.

Zinc oxide nanoparticles (ZnO-NPs) were synthesized using ginger (Zingiber officinale) extracts in a green synthesis approach and evaluated their in vitro cytotoxicity effect on the MDA-MB 231 breast cancer cell line. The bottom-up approach was employed to develop the green-synthesized ginger-encapsulated ZnO-NPs (GZnO-NPs) without using hazardous substances. The most substantial Fourier-transform infrared absorption peak of the ginger root extract was seen at 1634.24 cm-1. The peak also confirmed the presence of ginger root extract-encapsulated ZnO-NPs at 1556.79, 1471.54, and 1019.83 cm-1. It indicates that the biomolecules found in plant extracts behave as capping agents, aiding in the formation of nanoparticles. The mean particle sizes (PSs) of optimized GZnO-NPs of the ratios 1:2 were found to be 104.01 ± 7.12 nm with a zeta potential of -11.5 ± 1.31 mV. The X-ray diffraction and scanning electron microscope analysis confirmed that the prepared nanoparticles were spherical and crystalline, with PS ranging from 100 to 150 nm. The GZnO-NPs were subjected to MTT assay and cellular migration potential, and it was found that the inhibitory concentration on the MDA-MB 231 (breast) cancer cell line and scratch area showed a dose-dependent efficacy. The successfully green-synthesized GZnO-NPs effectively induced cell death in the MDA-MB 231 cancer cell line. The scratch assay results confirmed that prepared GZnO-NPs inhibited the proliferation and migration of cancerous cells.

Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats.

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.

Development and Evaluation of Topical Zinc Oxide Nanogels Formulation Using Dendrobium anosmum and Its Effect on Acne Vulgaris.

Zinc oxide nanoparticles have high levels of biocompatibility, a low impact on environmental contamination, and suitable to be used as an ingredient for environmentally friendly skincare products. In this study, biogenically synthesized zinc oxide nanoparticles using Dendrobium anosum are used as a reducing and capping agent for topical anti-acne nanogels, and the antimicrobial effect of the nanogel is assessed on Cutibacterium acne and Staphylococcus aureus. Dendrobium anosmum leaf extract was examined for the presence of secondary metabolites and its total amount of phenolic and flavonoid content was determined. Both the biogenically and chemogenic-synthesized zinc oxide nanoparticles were compared using UV-Visible spectrophotometer, FE-SEM, XRD, and FTIR. To produce the topical nanogel, the biogenic and chemogenic zinc oxide nanoparticles were mixed with a carbomer and hydroxypropyl-methyl cellulose (HPMC) polymer. The mixtures were then tested for physical and chemical characteristics. To assess their anti-acne effectiveness, the mixtures were tested against C. acne and S. aureus. The biogenic zinc oxide nanoparticles have particle sizes of 20 nm and a high-phase purity. In comparison to chemogenic nanoparticles, the hydrogels with biogenically synthesized nanoparticles was more effective against Gram-positive bacteria. Through this study, the hybrid nanogels was proven to be effective against the microbes that cause acne and to be potentially used as a green product against skin infections.

Green synthesis of chitosan/silver nanocomposite using kaempferol for triple negative breast cancer therapy and antibacterial activity.

The synthesis of polymer-encapsulated metal nanoparticles is a growing field of area due to their long-term uses in the development of new technologies. The present study describes the synthesis of chitosan/silver nanocomposite using kaempferol for anticancer and bactericidal activity. The formation of Kf-CS/Ag nanocomposite was confirmed by the development of a brown color and UV-absorbance around 438 nm. The IR study was utilized to determine the existence of Kf and CS in the synthesized nanocomposite. TEM analysis demonstrated that the synthesized nanocomposite have a predominantly uniform spherical shape and size ranges 7-10 nm. EDX spectrum showed the existence of Ag, C, and N elements in the nanocomposite material. Further, Kf-CS/Ag nanocomposite exhibited potential in vitro inhibitory property against triple-negative breast cancer (TNBC) cells and their IC50 values was found to be 53 µg/mL. Moreover, fluorescent assays such as DAPI and AO/EtBr confirmed the apoptosis induction ability of Kf-CS/Ag nanocomposite in MDA-MB-231 cells. The synthesized Kf-CS/Ag nanocomposite showed significant and dose-depended antibacterial property against S. aureus and P. aeruginosa. Thus, the obtained findings demonstrated that the synthesized nanocomposite can be potentially used to improve human health as biocidal nanocomposite in biomedical sectors.

Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract.

Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.

Acupuncture combined with auricular acupressure for smoking cessation and its effects on tobacco dependence and smoking behavior among Hong Kong smokers: a multicenter pilot clinical study.

BACKGROUND: Acupuncture combined with auricular acupressure has been used as a complementary and alternative treatment for smoking cessation in Hong Kong for over 10 years. This study aimed to investigate the success rates of smoking cessation posttreatment, and to evaluate treatment effects on tobacco dependence, smoking behavior, anxiety levels, and sleep disturbances between successful and unsuccessful quit smokers in Hong Kong. METHODS: This prospective, multicenter clinical study conducted between September 2020 and February 2022 in Hong Kong was part of the Guangdong-Hong Kong-Macau Greater Bay Area project on smoking cessation. Thirty eligible current smokers (mean age 47.10 years; 40% female) were recruited and received a combination of standardized acupuncture and auricular acupressure treatments twice weekly for 8 weeks. The primary outcome was the success rate of smoking cessation at week 24. The secondary outcomes were the success rates of smoking cessation at weeks 8 and 16, exhaled carbon monoxide (CO) levels, and changes in scores on the Fagerström Test for Nicotine Dependence (FTND), Autonomy Over Smoking Scale (AUTOS), Hamilton Anxiety Rating Scale (HAM-A), Self-rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI). Adverse events were also recorded. RESULTS: Of 30 eligible participants, 28 completed 6 or more treatment sessions; all completed follow-up assessments. At week 24, the success rate of smoking cessation was 46.67%. The successfully quit rates at weeks 8 and 16 were 36.67% and 43.33%, respectively. The overall change in mean FTND scores from baseline improved significantly from weeks 2 to 24 (P < 0.05), with the successful quit group showing significantly greater improvement between weeks 8 and 24 (P < 0.01). Compared with baseline values, there were significant reductions in mean AUTOS scores from weeks 6 to 24 (P < 0.001), with the successful quit group showing greater improvement at weeks 16 (P = 0.04) and 24 (P < 0.001). No significant changes were detected in exhaled CO levels or HAM-A, SAS, and PSQI scores. No study-related adverse events were observed. CONCLUSIONS: Acupuncture combined with auricular acupressure could be an effective alternative treatment for smoking cessation and reduction of tobacco dependence among Hong Kong smokers. Trial registration Chinese Clinical Trial Registry, No. ChiCTR2000033650. Registered on June 7, 2020. http://www.chictr.org.cn/showproj.aspx?proj=54866.

Functional effects of berberine in modulating mitochondrial dysfunction and inflammatory response in the respective amyloidogenic cells and activated microglial cells - In vitro models simulating Alzheimer's disease pathology.

AIM: Berberine (BBR) is an alkaloid extracted from Coptidis Rhizoma, also known as Huang-Lian. Huang-Lian has been used extensively in traditional Chinese medicine for the treatment of various diseases, including diabetes and dementia. Because Alzheimer's disease (AD) is a complex disease that involves various pathophysiological changes, the diverse neuroprotective effects of BBR may be useful for improving the brain's energy state at an early stage of the disease. MAIN METHODS: We performed extracellular flux and 1H NMR-based metabolic profiling analyses to investigate the effects of BBR on metabolic processes in these cells. Pioglitazone (PIO), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist has been studied extensively for the treatment of AD. We explored the combination dosing effects of BBR and PIO in vitro, then leveraged computational methods to explain the experimental finding. KEY FINDINGS: BBR demonstrates potential in modulating the mitochondrial bioenergetics and attenuating dysfunction of the primary energy and glutathione metabolism pathways in an AD cell model. It also suppresses basal respiration and reduces the production of pro-inflammatory cytokines in activated microglial cells. Both experimental and computational observations indicate that BBR and PIO have comparable binding affinities to the PPARγ protein, suggesting both drugs may have some overlapping effects for AD. SIGNIFICANCE: BBR exerts beneficial effects on disrupted metabolic processes in amyloidogenic cells and activated microglial cells, which are important for preventing or delaying early-stage disease progression. The choice of BBR or PIO for AD treatment depends on their respective pharmacokinetic profiles, delivery, efficacy and safety, and warrants further study.

Ancillary palm oil fuel ash (POFA) in sequencing batch reactor for enhancing recalcitrant pollutants removal from domestic wastewater.

Domestic wastewater has been generated massively along with rapid growth of population and economic. Biological treatment using sequencing batch reactor (SBR) augmented with palm oil fuel ash (POFA) was investigated for the first time. The performance of POFA in enhancing biological treatment of wastewater has not been tested. The porosity property of POFA can improve SBR efficiency by promoting growth of mixed liquor suspended solids (MLSS) and formation of larger flocs for settling and facilitating attachment of microorganisms and pollutants onto POFA surfaces. The properties of POFA were tested to identify morphological properties, particle size, surface area, chemical compositions. Four SBRs, namely SBR1, SBR2, SBR3 and SBR4 were provided with aeration rate of 1, 2, 3 and 4 L/min, respectively. Each reactor was augmented with different dosages of POFA. Optimum aeration rate and POFA concentration were identified by the performance of SBRs in removing chemical oxygen demand (COD), ammoniacal nitrogen (NH3-N) and colour from domestic wastewater. The results showed the most efficient COD (97.8%), NH3-N (99.4%) and colour (98.8%) removals were achieved at optimum POFA concentration of 4 g/L in SBR and aeration rate of 1 L/min. The study also found that higher aeration rate would contribute to the smaller specific size of flocs and decrease the pollutant removal efficiency.

In Vitro and In Vivo Comparison of Curcumin-Encapsulated Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles and Curcumin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complexes Administered Intranasally as Therapeutic Strategies for Alzheimer's Disease.

Curcumin (CUR) has antioxidant and anti-inflammatory effects that are beneficial to Alzheimer's disease (AD). However, the poor solubility and high instability of CUR compromise its application greatly. In this study, CUR-encapsulated chitosan-coated poly (lactic-co-glycolic acid) nanoparticles (CUR-CS-PLGA-NPs) and hydroxypropyl-ß-cyclodextrin-encapsulated CUR complexes (CUR/HP-ß-CD inclusion complexes) were developed and compared through intranasal administration. In vitro studies indicated that CUR in CUR/HP-ß-CD inclusion complexes was stable under physiological conditions over 72 h with 95.41 ± 0.01% remaining, which was higher than 49.66 ± 3.91% remaining in CUR-CS-PLGA-NPs. Meanwhile, CUR/HP-ß-CD inclusion complexes showed a higher cellular uptake level of CUR than CUR-CS-PLGA-NPs in SH-SY5Y cells. Both formulations could reduce CUR's cellular cytotoxicity and showed a comparable antioxidant effect. Both formulations displayed the anti-inflammatory effect at 20 µM CUR in BV-2 cells, which decreased TNF-α and IL-6 levels to approximately 70 and 40%, respectively, when compared to the positive control, respectively. In vivo pharmacokinetic studies indicated that after intranasal administration, the AUC values of CUR in the plasma and brain of the CUR/HP-ß-CD inclusion complex group were 2.57-fold and 1.12-fold higher than those in the CUR-CS-PLGA-NP group at the same dose of 2 mg/kg, respectively. In conclusion, CUR/HP-ß-CD inclusion complexes displayed better properties than CUR-CS-PLGA-NPs as a carrier for intranasal delivery of CUR for application in AD.

Investigation on the performance of hybrid anaerobic membrane bioreactors for fouling control and biogas production in palm oil mill effluent treatment.

Three different sizes of powdered activated carbon (PAC) were added in hybrid anaerobic membrane bioreactors (AnMBRs) and their performance was compared with a conventional AnMBR without PAC in treating palm oil mill effluent. Their working volume was 1 L each. From the result, AnMBRs with PAC performed better than the AnMBR without PAC. It was also found that adding a relatively smaller size of PAC (approximately 100 µm) enhanced the chemical oxygen demand removal efficiency to 78.53 ± 0.66%, while the concentration of mixed liquor suspended solid and mixed liquor volatile suspended solid were 8,050 and 6,850 mg/L, respectively. The smaller size of PAC could also enhance the biofloc formation and biogas production. In addition, the smaller particle sizes of PAC incorporated into polyethersulfone membrane resulted in higher performance of membrane fouling control and produced better quality of effluent as compared to the membrane without the addition of PAC.

Effects of metal-contaminated soils on the accumulation of heavy metals in gotu kola (Centella asiatica) and the potential health risks: a study in Peninsular Malaysia.

Centella asiatica is a commonly used medicinal plant in Malaysia. As heavy metal accumulation in medicinal plants which are highly consumed by human is a serious issue, thus the assessment of heavy metals in C. asiatica is important for the safety of consumers. In this study, the heavy metal accumulation in C. asiatica and the potential health risks were investigated. Samples of C. asiatica and surface soils were collected from nine different sites around Peninsular Malaysia. The concentration of six heavy metals namely Cd, Cu, Ni, Fe, Pb and Zn were determined by air-acetylene flame atomic absorption spectrophotometer (AAS). The degree of anthropogenic influence was assessed by calculating the enrichment factor (EF) and index of geoaccumulation (Igeo). The heavy metal uptake into the plant was estimated through the calculation of translocation factor (TF), bioconcentration factor (BCF) and correlation study. Estimated daily intakes (EDI) and target hazard quotients (THQ) were used to determine the potential health risk of consuming C. asiatica. The results showed that the overall surface soil was polluted by Cd, Cu and Pb, while the uptake of Zn and Ni by the plants was high. The value of EDI and THQ showed that the potential of Pb toxicity in C. asiatica was high as well. As heavy metal accumulation was confirmed in C. asiatica, daily consumption of the plant derived from polluted sites in Malaysia was not recommended.

Examining the protective effects of mindfulness training on working memory capacity and affective experience.

We investigated the impact of mindfulness training (MT) on working memory capacity (WMC) and affective experience. WMC is used in managing cognitive demands and regulating emotions. Yet, persistent and intensive demands, such as those experienced during high-stress intervals, may deplete WMC and lead to cognitive failures and emotional disturbances. We hypothesized that MT may mitigate these deleterious effects by bolstering WMC. We recruited 2 military cohorts during the high-stress predeployment interval and provided MT to 1 (MT, n = 31) but not the other group (military control group, MC, n = 17). The MT group attended an 8-week MT course and logged the amount of out-of-class time spent practicing formal MT exercises. The operation span task was used to index WMC at 2 testing sessions before and after the MT course. Although WMC remained stable over time in civilians (n = 12), it degraded in the MC group. In the MT group, WMC decreased over time in those with low MT practice time, but increased in those with high practice time. Higher MT practice time also corresponded to lower levels of negative affect and higher levels of positive affect (indexed by the Positive and Negative Affect Schedule). The relationship between practice time and negative, but not positive, affect was mediated by WMC, indicating that MT-related improvements in WMC may support some but not all of MT's salutary effects. Nonetheless, these findings suggest that sufficient MT practice may protect against functional impairments associated with high-stress contexts.

Factors affecting outcomes in colonoscopy.

There are many factors that influence successful outcomes in colonoscopy. The aims of this study were to evaluate these factors and determine ways to improve outcomes. All participants (N=229) who underwent planned colonoscopy between July and September 2004 were retrospectively included. Participants included 118 men and 111 women with a mean age of 59 years. Completion rate was 92%. Reasons of failure included poor bowel preparation (2.2%, p< .025), bowel looping (2.2%, p< .025), participant discomfort (1.3%), and obstructing lesion (1.3%). Mean midazolam dose was 3.8 mg. Three participants (1.3%) had midazolam alone, and all had complete colonoscopy. One hundred thirty-three participants (60.7%) had additional meperidine, with a completion rate of 94%. Eighty three participants (37.9%) had additional meperidine and Buscopan, with a completion rate reduced to 89.2%. There was no correlation between sedatives used and completion rate. Completion rate of colonoscopy in our unit was acceptable at 92%. A combination of midazolam and meperidine gave the best completion rates (94%). The two main reasons for incompletion were poor bowel preparation and excessive bowel looping.

p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy.

Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy. By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy (P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients (P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression (P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.