Fabrication of bio-inspired carbon nanodot-corn starch nanocomposite films via extrusion process for sustainable active food packaging applications.

In this study, carbon nanodot (CD)-corn starch (CS) nanocomposite films are fabricated for active food packaging applications. First, ginkgo biloba leaves (GBL) were used as a biomass-derived carbon precursor, and a facile hydrothermal method was employed to synthesise environmentally sustainable CDs. The GBL-derived carbon nanodots (gCDs) were then characterised and incorporated into a CS matrix via an extrusion process to fabricate the CS/gCD nanocomposite film. The effects of various gCD concentrations on the physicochemical and functional properties of CS/gCD composite films were systematically investigated. The gCD exhibited non-cytotoxic effect against human colorectal adenocarcinoma cell line (Caco-2) cells when exposed up to 1000 µg/mL. The incorporation of gCDs into the CS film improved its mechanical properties, with the toughness of the CS/gCD2% nanocomposite film exhibiting 198 % superiority compared to the CS film. In addition, the oxygen barrier and UV-blocking properties were significantly improved. Furthermore, the CS/gCD nanocomposite film significantly extended the shelf life of ω-3 oils owing to the superior antioxidant activity of the gCDs, exhibiting only 9 meq/kg during the 15-day storage period. Our results suggest that the developed CS/gCD active composite film is a promising candidate for environmentally sustainable solutions to enhance food shelf life and reduce food waste.

Novel insights into regulators and functional modulators of adipogenesis.

Adipogenesis is a process that differentiates new adipocytes from precursor cells and is tightly regulated by several factors, including many transcription factors and various post-translational modifications. Recently, new roles of adipogenesis have been suggested in various diseases. However, the molecular mechanisms and functional modulation of these adipogenic genes remain poorly understood. This review summarizes the regulatory factors and modulators of adipogenesis and discusses future research directions to identify novel mechanisms regulating adipogenesis and the effects of adipogenic regulators in pathological conditions. The master adipogenic transcriptional factors PPARγ and C/EBPα were identified along with other crucial regulatory factors such as SREBP, Kroxs, STAT5, Wnt, FOXO1, SWI/SNF, KLFs, and PARPs. These transcriptional factors regulate adipogenesis through specific mechanisms, depending on the adipogenic stage. However, further studies related to the in vivo role of newly discovered adipogenic regulators and their function in various diseases are needed to develop new potent therapeutic strategies for metabolic diseases and cancer.

Bee (Apis mellifera L. 1758) wax restores adipogenesis and lipid accumulation of 3T3-L1 cells in cancer-associated cachexia condition.

Cachexia is associated with various diseases, such as heart disease, infectious disease, and cancer. In particular, cancer-associated cachexia (CAC) accounts for more than 20% of mortality in cancer patients worldwide. Adipose tissue in CAC is characterized by adipocyte atrophy, mainly due to excessively increased lipolysis and impairment of adipogenesis. CAC is well known for the loss of skeletal muscle mass and/or fat mass. CAC induces severe metabolic alterations, including protein, lipid, and carbohydrate metabolism. The objectives of this study were to evaluate the effects of bee wax (Apis mellifera L. 1758) (BW) extract on adipogenesis, lipolysis, and mitochondrial oxygen consumption through white adipocytes, 3T3-L1. To achieve this study, cancer-associated cachexia condition was established by incubation of 3T3-L1 with colon cancer cell line CT26 cultured media. BW extract recovered the reduced adipogenesis under cachectic conditions in CT26 media. Treatment of BW showed increasing lipid accumulation as well as adipogenic gene expression and its target gene during adipogenesis. The administration of BW to adipocytes could decrease lipolysis. Also, BW could significantly downregulated the mitochondrial fatty acid oxidation-related genes, oxygen consumption rate, and extracellular acidification rate. Our results suggest that BW could improve metabolic disorders such as CAC through the activation of adipogenesis and inhibition of lipolysis in adipocytes, although we need further validation in vivo CAC model to check the effects of BW extract. Therefore, BW extract supplements could be useful as an alternative medicine to reverse energy imbalances.

Biomarkers of Cellular Senescence and Aging: Current State-of-the-Art, Challenges and Future Perspectives.

Population aging has increased the global prevalence of aging-related diseases, including cancer, sarcopenia, neurological disease, arthritis, and heart disease. Understanding aging, a fundamental biological process, has led to breakthroughs in several fields. Cellular senescence, evinced by flattened cell bodies, vacuole formation, and cytoplasmic granules, ubiquitously plays crucial roles in tissue remodeling, embryogenesis, and wound repair as well as in cancer therapy and aging. The lack of universal biomarkers for detecting and quantifying senescent cells, in vitro and in vivo, constitutes a major limitation. The applications and limitations of major senescence biomarkers, including senescence-associated ß-galactosidase staining, telomere shortening, cell-cycle arrest, DNA methylation, and senescence-associated secreted phenotypes are discussed. Furthermore, explore senotherapeutic approaches for aging-associated diseases and cancer. In addition to the conventional biomarkers, this review highlighted the in vitro, in vivo, and disease models used for aging studies. Further, technologies from the current decade including multi-omics and computational methods used in the fields of senescence and aging are also discussed in this review. Understanding aging-associated biological processes by using cellular senescence biomarkers can enable therapeutic innovation and interventions to improve the quality of life of older adults.

Gonadal efficacy of Thymus quinquecostatus Celakovski: Regulation of testosterone levels in aging mouse models.

Late-onset hypogonadism (LOH) is an age-related disease in men characterized by decreased testosterone levels with symptoms such as decreased libido, erectile dysfunction, and depression. Thymus quinquecostatus Celakovski (TQC) is a plant used as a volatile oil in traditional medicine, and its bioactive compounds have anti-inflammatory potential. Based on this knowledge, the present study aimed to investigate the effects of TQC extract (TE) on LOH in TM3 Leydig cells and in an in vivo aging mouse model. The aqueous extract of T. quinquecostatus Celakovski (12.5, 25, and 50 µg/mL concentrations) was used to measure parameters such as cell viability, testosterone level, body weight, and gene expression, via in vivo studies. Interestingly, TE increased testosterone levels in TM3 cells in a dose-dependent manner without affecting cell viability. Furthermore, TE significantly increased the expression of genes involved in the cytochrome P450 family (Cyp11a1, Cyp17a1, Cyp19a1, and Srd5a2), which regulate testosterone biosynthesis. In aging mouse models, TE increased testosterone levels without affecting body weight and testicular tissue weight tissue of an aging animal group. In addition, the high-dose TE-treated group (50 mg/kg) showed significantly increased expression of the cytochrome p450 enzymes, similar to the in vitro results. Furthermore, HPLC-MS analysis confirmed the presence of caffeic acid and rosmarinic acid as bioactive compounds in TE. Thus, the results obtained in the present study confirmed that TQC and its bioactive compounds can be used for LOH treatment to enhance testosterone production.

Spontaneous Fusion with Transformed Mesenchymal Stromal Cells Results in Complete Heterogeneity in Prostate Cancer Cells.

Tumor cells gain advantages in growth and survival by acquiring genotypic and phenotypic heterogeneity. Interactions with bystander cells in the tumor microenvironment contribute to the progression of heterogeneity. We have shown that fusion between tumor and bystander cells is one form of interaction, and that tumor-bystander cell fusion has contrasting effects. By trapping fusion hybrids in the heterokaryon or synkaryon state, tumor-bystander cell fusion prevents the progression of heterogeneity. However, if trapping fails, fusion hybrids will resume replication to form derivative clones with diverse genomic makeups and behavioral phenotypes. To determine the characteristics of bystander cells that influence the fate of fusion hybrids, we co-cultured prostate mesenchymal stromal cell lines and their spontaneously transformed sublines with LNCaP as well as HPE-15 prostate cancer cells. Subclones derived from cancer-stromal fusion hybrids were examined for genotypic and phenotypic diversifications. Both stromal cell lines were capable of fusing with cancer cells, but only fusion hybrids with the transformed stromal subline generated large numbers of derivative subclones. Each subclone had distinct cell morphologies and growth behaviors and was detected with complete genomic hybridization. The health conditions of the bystander cell compartment play a crucial role in the progression of tumor cell heterogeneity.

Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate.

Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors' inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC.

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

MicroRNAs：potential new targets for allergic diseases / 中国药理学通报

Allergic diseases such as allergic asthma, allergic der-matitis, allergic rhinitis, are polygenic diseases, involving the interaction between the environment, genes and immunity. In the past few decades, the incidence rate of allergic diseases in-creased predominantly and influenced the quality of people's lives seriously, so looking for new targets for the prevention and treat-ment of allergic diseases and drugs with less adverse reaction be-comes a hot topic for researchers. MicroRNAs(miRNAs)are a class of endogenous non-coding small RNAs that mediate nega-tively posttranscriptional regulation of gene expression by targe-ting specific mRNA sequences to inhibit the translation of mR-NAs. They are widely involved in the biological processes of cell differentiation, immune response and tumor development. The study shows that miRNAs can control the occurrence and devel-opment of allergic diseases. Studying the regulatory role of miR-NAs in allergic diseases has important implications for exploring the immunopathological mechanisms and discovering new thera-peutic targets of drugs.

Advances on abnormal expression of E-cadherin with bronchial asthma / 中国药理学通报

Bronchial asthma is a kind of respiratory disease which affects people 's life quality seriously. Many factors in-volved in the occurrence and development of such disease, of which the aberrant expression of E-cad plays a critical role in it. Research found that E-cad is an important cell adhesion molecu-lar, and its main function is to maintain the structural integrity of cells and participate in the improvement of airway remodeling as well as restoration of immune function. Further study showed that the role of mucosal barrier of airway epithelial cells in bronchial asthma patients was often damaged. Moreover, the protein ex-pression of E-cad decreased significantly in mucosal molecular, which suggested that the abnormal expression of E-cad was in-volved in the development of bronchial asthma. A review on the relations between the abnormal expression of E-cad protein and bronchial asthma has been discussed in this paper, also it in-cludes the discussion about the mechanisms of E-cad’ s disorder-induced bronchial asthma as well as explores the strategies of bronchial asthma treatment, which may provide references for the follow-up research and clinical treatment.