Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.

The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein-protein interactions, we also chose a collection of well-known functional protein partners for pleckstrin. Investigations were also carried out on the relationship between pleckstrins and other cancers regarding mutations and copy number alterations. The cumulative impact of pleckstrin and their associated genes on various cancers, Gene Ontology (GO), and pathway analyses were used for their evaluation. Thus, the expression profiles of PHLDA family members and their prognosis in various cancers may be revealed by this study. During this multiomics analysis, we found that among the PHLDA family, PHLDA1 may be a therapeutic target for several cancers, including kidney, colon, and brain cancer, while PHLDA2 can be a therapeutic target for cancers of the colon, esophagus, and pancreas. Additionally, PHLDA3 may be a useful therapeutic target for ovarian, renal, and gastric cancer.

Hydroponic Ginseng ROOT Mediated with CMC Polymer-Coated Zinc Oxide Nanoparticles for Cellular Apoptosis via Downregulation of BCL-2 Gene Expression in A549 Lung Cancer Cell Line.

The unique and tailorable physicochemical features of zinc oxide nanoparticles (ZnO-NPs) synthesized from green sources make them attractive for use in cancer treatment. Hydroponic-cultured ginseng-root-synthesized ZnO-NPs (HGRCm-ZnO NPs) were coated with O-carboxymethyl chitosan (CMC) polymer, which stabilized and enhanced the biological efficacy of the nanoparticles. Nanoparticles were characterized by X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and energy-dispersive X-ray spectroscopy (EDS). The flower-shaped nanoparticles were crystalline in nature with a particle size of 28 nm. To evaluate if these NPs had anti-lung cancer activity, analysis was performed on a human lung carcinoma cell line (A549). HGRCm-ZnO nanoparticles showed less toxicity to normal keratinocytes (HaCaTs), at concentrations up to 20 µg/mL, than A549 cancer cells. Additionally, these NPs showed dose-dependent colony formation and cell migration inhibition ability, which makes them more promising for lung cancer treatment. Additionally, Hoechst and propidium iodide dye staining also confirmed that the NP formulation had apoptotic activity in cancer cells. Further, to evaluate the mechanism of cancer cell death via checking the gene expression, HGRCm ZnO NPs upregulated the BAX and Caspase 3 and 9 expression levels but downregulated Bcl-2 expression, indicating that the nanoformulation induced mitochondrial-mediated apoptosis. Moreover, these preliminary results suggest that HGRCm ZnO NPs can be a potential candidate for future lung cancer treatment.

A Focused Review on Molecular Signalling Mechanisms of Ginsenosides Anti-Lung Cancer and Anti-inflammatory Activities.

BACKGROUND: Ginseng (Panax ginseng Meyer) is a cultivated medicinal herb that has been widely available in the Asian region since the last century. Ginseng root is used worldwide in Oriental medicine. Currently, the global mortality and infection rates for lung cancer and inflammation are significantly increasing. Therefore, various preventative methods related to the activity of ginsenosides have been used for lung cancer as well as inflammation. METHODS: Web-based searches were performed on Web of Science, Springer, PubMed, and Scopus. A cancer statistical analysis was also conducted to show the current ratio of affected cases and death from lung cancer around the world. RESULTS: Ginsenosides regulate the enzymes that participate in tumor growth and migration, such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), extracellular signalregulated kinases 1/2 (ERK1/2), the gelatinase network metalloproteinase-2 (MMP-2/9) and activator protein 1 (AP-1). In addition, ginsenosides also possess anti-inflammatory effects by inhibiting the formation of proinflammatory cytokines (tumor necrosis factor-α) (TNF-α) and interleukin-1ß (IL-1ß) and controlling the activities of inflammatory signalling pathways, such as NF-κB, Janus kinase2/signal transducer, and activator of transcription 3 (Jak2/Stat3). CONCLUSION: In several in vitro and in vivo models, P. ginseng showed potential beneficial effects in lung cancer and inflammation treatment. In this review, we provide a detailed and up-to-date summary of research evidence for antilung cancer and anti-inflammatory protective effects of ginsenosides and their potential molecular mechanisms.

Investigating the Anticancer Activity of G-Rh1 Using In Silico and In Vitro Studies (A549 Lung Cancer Cells).

Ginsenoside Rh1 (G-Rh1), a possible bioactive substance isolated from the Korean Panax ginseng Meyer, has a wide range of pharmacological effects. In this study, we have investigated the anticancer efficacy of G-Rh1 via in silico and in vitro methodologies. This study mainly focuses on the two metastatic regulators, Rho-associated protein kinase 1 (ROCK1) and RhoA, along with other standard apoptosis regulators. The ROCK1 protein is a member of the active serine/threonine kinase family that is crucial for many biological processes, including cell division, differentiation, and death, as well as many cellular processes and muscle contraction. The abnormal activation of ROCK1 kinase causes several disorders, whereas numerous studies have also shown that RhoA is expressed highly in various cancers, including colon, lung, ovarian, gastric, and liver malignancies. Hence, inhibiting both ROCK1 and RhoA will be promising in preventing metastasis. Therefore, the molecular level interaction of G-Rh1 with the ROCK1 and RhoA active site residues from the preliminary screening clearly shows its inhibitory potential. Molecular dynamics simulation and principal component analysis give essential insights for comprehending the conformational changes that result from G-Rh1 binding to ROCK1 and RhoA. Further, MTT assay was employed to examine the potential cytotoxicity in vitro against human lung cancer cells (A549) and Raw 264.7 Murine macrophage cells. Thus, G-Rh1 showed significant cytotoxicity against human lung adenocarcinoma (A549) at 100 µg/mL. In addition, we observed an elevated level of reactive oxygen species (ROS) generation, perhaps promoting cancer cell toxicity. Additionally, G-Rh1 suppressed the mRNA expression of RhoA, ROCK1, MMP1, and MMP9 in cancer cell. Accordingly, G-Rh1 upregulated the p53, Bax, Caspase 3, caspase 9 while Bcl2 is downregulated intrinsic pathway. The findings from our study propose that the anticancer activity of G-Rh1 may be related to the induction of apoptosis by the RhoA/ROCK1 signaling pathway. As a result, this study evaluated the functional drug-like compound G-Rh1 from Panax ginseng in preventing and treating lung cancer adenocarcinoma via regulating metastasis and apoptosis.

Pomegranate juice fermented by tannin acyl hydrolase and Lactobacillus vespulae DCY75 enhance estrogen receptor expression and anti-inflammatory effect.

Phenolics are phytochemicals in plants, fruits, and vegetables have potential health-promoting efficacies. However, mostly available as a complex form. So, to increase the contents and nutritional value of the phenolic compounds, fermentation is most readily used in the food industry. Especially, the hydrolyzable tannins present in the pomegranate that can be liberated into monomolecular substances, which enhances biological activity. Thus, this study aims to convert hydrolyzable tannins to ellagic acid by fermentation using Tannin acyl hydrolase (TAH) and a novel bacteria strain Lactobacillus vespulae DCY75, respectively to investigate its effect on Estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) mRNA expression along with inflammation inhibition. As a result, the fermentation enhanced the ellagic acid content up to 70% by the synergetic effect of TAH and DCY75. Furthermore, fermented pomegranate (PG-F) increased cellular proliferation as well as upregulated the gene expression of estrogen regulators such as ERα, ERß, and pS2 in breast cancer cell line (MCF-7), which commonly used to evaluate estrogenic activity. Moreover, to study the inflammation associated with low estrogen in menopause, we have analyzed the inhibition of nitric oxide (NO)/inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. The PG-F juice did not exert any cytotoxicity in RAW 264.7 cells and inhibited NO production along with the downregulation of a major pro-inflammatory cytokine iNOS which indicates the anti-inflammatory potential of it. To sum it up, the fermented commercial pomegranate juice using a novel bacteria strain increased the amount of ellagic acid that the value added bioactive of pomegranate and it has significantly increased the estrogenic activity via upregulating estrogen related biomarkers expression and reduced the risk of related inflammation via NO/iNOS inhibition. This study could be a preliminary study to use fermented pomegranate as a potential health functional food after further evaluation.

Binary Effects of Gynostemma Gold Nanoparticles on Obesity and Inflammation via Downregulation of PPARγ/CEPBα and TNF-α Gene Expression.

Nanoscience is a multidisciplinary skill with elucidated nanoscale particles and their advantages in applications to various fields. Owing to their economical synthesis, biocompatible nature, and widespread biomedical and environmental applications, the green synthesis of metal nanoparticles using medicinal plants has become a potential research area in biomedical research and functional food formulations. Gynostemma pentaphyllum (GP) has been extensively used in traditional Chinese medicine to cure several diseases, including diabetes mellitus (DM). This is the first study in which we examined the efficacy of G. pentaphyllum gold nanoparticles (GP-AuNPs) against obesity and related inflammation. GP extract was used as a capping agent to reduce Au2+ to Au0 to form stable gold nanoparticles. The nanoparticles were characterized by using UV-VIS spectroscopy, and TEM images were used to analyze morphology. In contrast, the existence of the functional group was measured using FTIR, and size and shape were examined using XRD analysis. In vitro analysis on GP-AuNPs was nontoxic to RAW 264.7 cells and 3T3-L1 cells up to a specific concentration. It significantly decreased lipid accumulation in 3T3-L1 obese and reduced NO production in Raw 264.7 macrophage cells. The significant adipogenic genes PPARγ and CEPBα and a major pro-inflammatory cytokine TNF-α expression were quantified using RT-PCR. The GP-AuNPs decreased the face of these genes remarkably, revealing the antiadipogenic and anti-inflammatory activity of our synthesized GP-AuNPs. This study represents thorough research on the antiobesity effect of Gynostemma pentaphyllum gold nanoparticles synthesized using a green approach and the efficacy instead of related inflammatory responses.

Role of Ginsenosides in Browning of White Adipose Tissue to Combat Obesity: A Narrative Review on Molecular Mechanism.

BACKGROUND AND AIMS: Adipose tissue play an important role in the regulation of energy balance and homeostasis. Two main types of adipose tissue are found in mammals, white adipose tissue (WAT) and brown adipose tissue (BAT). WAT acts as energy storage in the form of triglycerides; excess WAT is a cause of overweight and obesity. Conversely, BAT works by dissipating energy as heat, which may facilitate the suppression of obesity and play a vital role in maintaining core body temperature. Recently a new type of adipocyte has been introduced: beige or brite adipocytes. This adipocyte has morphological and functional similarities to BAT but, developmentally, it is more closely related to WAT. In response to appropriate stimuli, WAT deposits can take on characteristics like BAT and act as beige or brite adipocyte, through a process called "browning." Browning has become a promising therapeutic target for obesity due to its fat-burning potential. METHODS: Searches were carried out using MEDLINE/PubMed, Scopus, and Web of Science. The in vivo and in vitro mechanisms of ginsenosides related to beige adipocytes were also included. RESULTS: In this review, we found a considerable number of articles suggesting that the anti-obesity action of ginsenosides might be related to WAT browning and discussed the possible mechanisms for this. CONCLUSION: Current evidence from the in vitro and in vivo studies strongly supports that ginsenosides may play a significant role in the browning of WAT. The browning effects of ginsenosides are associated with various signaling pathways, markers, and transcription factors. In conclusion, ginsenosides may help counteract obesity by promoting the browning of WAT.

Hydroponic Cultured Ginseng Leaves Zinc Oxides Nanocomposite Stabilized with CMC Polymer for Degradation of Hazardous Dyes in Wastewater Treatment.

This study demonstrated the synthesis of o-carboxymethyl chitosan (CMC)-stabilized zinc oxide nanocomposites (ZnO NCs) combined with aqueous leaves extracts of hydroponically cultured ginseng and used as a photocatalyst for the degradation of hazardous dyes, including malachite green (MG), rhodamine B (RB), and congo red (CR) under ultraviolet illumination. Hydroponic ginseng leaves contain bioactive components, namely ginsenoside and natural polyphenol, which prompt ginseng's biological effect. Besides, the CMC polymer is naturally biodegradable, stabilizes the nanoformation and enhances the solubility of ginsenoside. The hydroponic ginseng leaves zinc oxide CMC nanocomposites (GL-CMC-ZnO NCs) were synthesized using the co-precipitation method and characterized using different analytical methods. The FTIR analysis identified significant phytochemicals in the leaves extracts and cotton-shape morphology observed using FE-TEM analysis. The XRD analysis also determined that the crystallite size was 28 nm. The photocatalyst degraded CR, RB, and MG dyes by approximately 87%, 94%, and 96% within contact times of 10, 20, 25, and 30 min, respectively, when the dye concentration was 15 mg/L. As far as our knowledge, this is the first report on hydroponic ginseng NCs incorporated with the CMC polymer for the degradation of hazardous dyes on wastewater treatment. This study can add significant value to large-scale wastewater treatment.

Enhanced Antiobesity Efficacy of Tryptophan Using the Nanoformulation of Dendropanax morbifera Extract Mediated with ZnO Nanoparticle.

Green synthesis of metal nanoparticles from medicinal plants has provided a broad scope in biomedical research and functional food formulations due to low toxicity. Dendropanax morbifera (DM) is a versatile traditional medicine used for various inflammatory diseases due to its extensive antioxidant activity. We investigated DM as a natural capping agent for Zn2+ ions and coloaded it with tryptophan for its penetration and antiobesity behavior. DM zinc oxide nanoparticles (DM-ZnO NPs) were prepared and then entrapped with tryptophan (DM-ZnO-Try nanoemulsion (NE)) for stable formulation using the O/W nanoemulsion method. The hydrodynamic sizes measured by dynamic light scattering for DM-ZnO NPs and DM-ZnO-Try NE are about 146.26 ± 3.31 and 151.16 ± 3.59 nm, respectively. TEM and SEM reveal its morphology. In vitro analysis on both NPs and NE was non-toxic to RAW 264.7 and 3T3-L1 preadipocyte cell line. It significantly reduced the accumulated lipids through lipolysis performed at 10 ug/mL in 3T3-L1 preadipocyte cells. NE suppresses the differentiation of 3T3-L1 adipocytes and lowers triglycerides. Further, the substantial reduction of lipid content is evident with Oil Red O staining and OD measurement. In this present study, the synergetic effect of DM-ZnO NPs and tryptophan is reported, which provides a way for more detailed research on its efficacy for obesity and obesity-associated disorders.

Panos-Fermented Extract-Mediated Nanoemulsion: Preparation, Characterization, and In Vitro Anti-Inflammatory Effects on RAW 264.7 Cells.

This study focused on developing Panos nanoemulsion (P-NE) and enhancing the anti-inflammatory efficacy for the treatment of inflammation. The effects of P-NE were evaluated in terms of Nitric oxide (NO production) in Lipopolysaccharide (LPS), induced RAW 264.7 cells, Reactive oxygen species (ROS) generation using Human Keratinocyte cells (HaCaT), and quantitative polymerase chain reaction (qPCR) analysis. Sea buckthorn oil, Tween 80, and span 80 were used and optimize the process. Panos extract (P-Ext) was prepared using the fermentation process. Further high-energy ultra-sonication was used for the preparation of P-NE. The developed nanoemulsion (NE) was characterized using different analytical methods. Field emission transmission electron microscopy (FE-TEM) analyzed the spherical shape and morphology. In addition, stability was analyzed by Dynamic light scattering (DLS) analysis, where particle size was analyzed 83 nm, and Zeta potential -28.20 ± 2 (mV). Furthermore, 90 days of stability was tested using different temperatures conditions where excellent stability was observed. P-NE are non-toxic in (HaCaT), and RAW264.7 cells up to 100 µg/mL further showed effects on ROS and NO production of the cells at 50 µg/mL. The qPCR analysis demonstrated the suppression of pro-inflammatory mediators for (Cox 2, IL-6, IL-1ß, and TNF-α, NF-κB, Ikkα, and iNOS) gene expression. The prepared NE exhibited anti-inflammatory effects, demonstrating its potential as a safe and non-toxic nanomedicine.

Cordyceps militaris Fungus Extracts-Mediated Nanoemulsion for Improvement Antioxidant, Antimicrobial, and Anti-Inflammatory Activities.

This study aimed to produce and optimize a Cordyceps militaris-based oil-in-water (O/W) nanoemulsion (NE) encapsulated in sea buckthorn oil (SBT) using an ultrasonication process. Herein, a nonionic surfactant (Tween 80) and chitosan cosurfactant were used as emulsifying agents. The Cordyceps nanoemulsion (COR-NE) was characterized using Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and field-emission transmission electron microscope (FE-TEM). The DLS analyses revealed that the NE droplets were 87.0 ± 2.1 nm in diameter, with a PDI value of 0.089 ± 0.023, and zeta potential of -26.20 ± 2. The small size, low PDI, and stable zeta potential highlighted the excellent stability of the NE. The NE was tested for stability under different temperature (4 °C, 25 °C, and 60 °C) and storage conditions for 3 months where 4 °C did not affect the stability. Finally, in vitro cytotoxicity and anti-inflammatory activity were assessed. The results suggested that the NE was not toxic to RAW 264.7 or HaCaT (human keratinocyte) cell lines at up to 100 µL/mL. Anti-inflammatory activity in liposaccharides (LPS)-induced RAW 264.7 cells was evident at 50 µg/mL and showed inhibition of NO production and downregulation of pro-inflammatory gene expression. Further, the NE exhibited good antioxidant (2.96 ± 0.10 mg/mL) activity and inhibited E. coli and S. aureus bacterial growth. Overall, the COR-NE had greater efficacy than the free extract and added significant value for future biomedical and cosmetics applications.

Ecofriendly Synthesis of Silver Nanoparticles by Terrabacter humi sp. nov. and Their Antibacterial Application against Antibiotic-Resistant Pathogens.

It is essential to develop and discover alternative eco-friendly antibacterial agents due to the emergence of multi-drug-resistant microorganisms. In this study, we isolated and characterized a novel bacterium named Terrabacter humi MAHUQ-38T, utilized for the eco-friendly synthesis of silver nanoparticles (AgNPs) and the synthesized AgNPs were used to control multi-drug-resistant microorganisms. The novel strain was Gram stain positive, strictly aerobic, milky white colored, rod shaped and non-motile. The optimal growth temperature, pH and NaCl concentration were 30 °C, 6.5 and 0%, respectively. Based on 16S rRNA gene sequence, strain MAHUQ-38T belongs to the genus Terrabacter and is most closely related to several Terrabacter type strains (98.2%-98.8%). Terrabacter humi MAHUQ-38T had a genome of 5,156,829 bp long (19 contigs) with 4555 protein-coding genes, 48 tRNA and 5 rRNA genes. The culture supernatant of strain MAHUQ-38T was used for the eco-friendly and facile synthesis of AgNPs. The transmission electron microscopy (TEM) image showed the spherical shape of AgNPs with a size of 6 to 24 nm, and the Fourier transform infrared (FTIR) analysis revealed the functional groups responsible for the synthesis of AgNPs. The synthesized AgNPs exhibited strong anti-bacterial activity against multi-drug-resistant pathogens, Escherichia coli and Pseudomonas aeruginosa. Minimal inhibitory/bactericidal concentrations against E. coli and P. aeruginosa were 6.25/50 and 12.5/50 µg/mL, respectively. The AgNPs altered the cell morphology and damaged the cell membrane of pathogens. This study encourages the use of Terrabacter humi for the ecofriendly synthesis of AgNPs to control multi-drug-resistant microorganisms.

Dendropanax Morbifera Extract-Mediated ZnO Nanoparticles Loaded with Indole-3-Carbinol for Enhancement of Anticancer Efficacy in the A549 Human Lung Carcinoma Cell Line.

Dendropanax morbifera is a versatile plant that has been used as a herbal medicine due to its various useful medicinal effects. To protect its active component from biological stress and increase its drug efficacy as well as drug bioavailability, nanoemulsion was prepared. Dendropanax morbifera zinc oxide nanoparticles (DM-ZnO NPs) were synthesized using the plant extract via the co-precipitation method and loaded with active indole-3-carbinol for nanoemulsion formulation using the ultrasonication process. Field emission transmission electron microscope revealed the flower shape of the Dendropanax morbifera indole-3-carbinol zinc oxide nanoemulsion (DM-ZnO-I3C-NE). In contrast, DM-ZnO NPs showed a spheroid shape that coincides agreeably with field emission electron scanning microscope. The hydrodynamic sizes by dynamic light scattering are about 65 ± 3 nm and 239.6 ± 6 nm and the crystallite sizes from X-ray diffraction are 11.52 nm and 16.07 nm for DM-ZnO NPs and DM-ZnO-I3C-NE, respectively. In vitro analysis revealed the cytotoxicity of DM-ZnO-I3C-NE against a human lung cancer cell line (A549) at 12.5 µg/mL as well as reactive oxygen species (ROS) production. The DM-ZnO-I3C-NE-induced ROS generation level was higher than that of DM-ZnO NPs and free indole-3-carbinol. The synergistic effect of DM-ZnO and indole-3-carbinol indicates DM-ZnO-I3C-NE as a potential candidate for future lung cancer drug and could be scope for functional food.

Synthesis of a Zinc Oxide Nanoflower Photocatalyst from Sea Buckthorn Fruit for Degradation of Industrial Dyes in Wastewater Treatment.

: Green synthesis of ZnO nanoparticles has attracted research attention as a sustainable method of avoiding the destructive effect of chemicals. We synthesized a flower-shaped zinc oxide (ZnO) nanoflower (NF) from sea buckthorn fruit (SBT) by co-precipitation and characterized it using X-ray powder diffraction (XRD), X-ray photo electronic microscopy (XPS), photoluminescence (PL), field emission transmission electron microscopy (FE-TEM), and Fourier-transform infrared (FT-IR) spectroscopy. The ability of the ZnO/NF to degrade cationic and anionic dyes, including malachite green (MG), Congo red (CR), methylene blue (MB), and eosin Y (EY), under ultraviolet illumination was studied. The photocatalyst degraded approximately 99% of the MG, MB, CR and EY dyes within 70, 70, 80, and 90 min of contact time, respectively, at a dye concentration of 15 mg/L, 5 mg/L, SBT-ZnO/NF degraded 100% of the MG, MB, CR and EY dyes within 23, 25, 28, and 30 min, respectively. The results indicate that SBT-ZnO/NFs as synthesized is an inexpensive, non-toxic, rapid, and reusable photocatalyst that can play an enhanced role in wastewater treatment.

Synthesis of panos extract mediated ZnO nano-flowers as photocatalyst for industrial dye degradation by UV illumination.

Green synthesis of zinc oxide has gained extensive attention as a reliable, sustainable, and eco-friendly protocol to reduce the destructive effects associated with the traditional synthesis methods commonly utilized in laboratory and industry. Here for the first time, we have synthesized quaker ladies flower type ZnO (ZnO/QNF) from panos extract (extract from four panax plants such as Panax ginseng, Acanthopanax senticosus, Kalopanax septemlobus and Dendropanax morbifera). The synthesized ZnO materials was characterized using powder X-ray diffraction, Fourier infrared spectroscopy, X-ray photoelectron spectroscopy and Transmission electron microscope. The newly synthesized ZnO/QNF was applied for the removal of industrial dyes such as methylene blue (MB), Eosin Y (EY) and Malachite green (MG) under UV illumination. The photocatalyst degraded the 15 mg L-1 MB, EY and MG to >99% within 80, 90 and 110 min of contact time, respectively. In addition, the ZnO/QNF photocatalyst removed the low concentrated 5 mg L-1 of MB, EY, and MG within 30, 35 and 40 min of contact time, respectively. The pedal structure provided all the active sites available for the easy interaction with dye molecule under UV, and that enabled fast kinetics of dye degradation than the many other benchmark materials reported previously. The ZnO photocatalyst could be reused minimum of five cycles without any significant loss in degradation efficiency.