Multicolumn Nanoflow Liquid Chromatography with Accelerated Offline Gradient Generation for Robust and Sensitive Single-Cell Proteome Profiling.

Peptide separations that combine high sensitivity, robustness, peak capacity, and throughput are essential for extending bottom-up proteomics to smaller samples including single cells. To this end, we have developed a multicolumn nanoLC system with offline gradient generation. One binary pump generates gradients in an accelerated fashion to support multiple analytical columns, and a single trap column interfaces with all analytical columns to reduce required maintenance and simplify troubleshooting. A high degree of parallelization is possible, as one sample undergoes separation while the next sample plus its corresponding mobile phase gradient are transferred into the storage loop and a third sample is loaded into a sample loop. Selective offline elution from the trap column into the sample loop prevents salts and hydrophobic species from entering the analytical column, thus greatly enhancing column lifetime and system robustness. With this design, samples can be analyzed as fast as every 20 min at a flow rate of just 40 nL/min with close to 100% MS utilization time and continuously for as long as several months without column replacement. We utilized the system to analyze the proteomes of single cells from a multiple myeloma cell line upon treatment with the immunomodulatory imide drug lenalidomide.

Unlocking the Therapeutic Potential of Marine Collagen: A Scientific Exploration for Delaying Skin Aging.

Aging is closely associated with collagen degradation, impacting the structure and strength of the muscles, joints, bones, and skin. The continuous aging of the skin is a natural process that is influenced by extrinsic factors such as UV exposure, dietary patterns, smoking habits, and cosmetic supplements. Supplements that contain collagen can act as remedies that help restore vitality and youth to the skin, helping combat aging. Notably, collagen supplements enriched with essential amino acids such as proline and glycine, along with marine fish collagen, have become popular for their safety and effectiveness in mitigating the aging process. To compile the relevant literature on the anti-aging applications of marine collagen, a search and analysis of peer-reviewed papers was conducted using PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1991 to 2024. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging by minimizing oxidative stress, photodamage, and the appearance of wrinkles. Various bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the topical application of hyaluronic acid is discussed as a mechanism to increase collagen production and skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in skin healing and bone regeneration applications. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Establishment and characterization of cisplatin-resistant cell lines from canine mammary gland tumors.

The development of cisplatin resistance is one of the major causes of mammary cancer treatment failure, and is associated with changes in Sox4 gene expression. To investigate the characteristic changes that occur in canine mammary gland tumor (CMGT) cells following the development of acquired cisplatin resistance, along with the relationship between these changes and the Sox4 gene. We constructed cisplatin-resistant cell line, CHMpCIS, from the cell line CHMp, which was isolated from the primary lesion of a malignant CMGT. The biological characteristics of these cells were examined by Western blot analysis, Transwell assays, and mammosphere formation assays. Compared to CHMp cells, CHMpCIS cells exhibited elevated cisplatin resistance, apoptotic escape ability, enhanced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features, in addition to over-activation of the Wnt/ß-catenin signaling pathway and increased Sox4 protein. In CMGT cases, CMGT tissues (CMGTT) expressed higher levels of Sox4 protein and mRNA compared to adjacent tissues (CAMGTT). We found that these changes were inhibited by silencing of Sox4 expression in CHMpCIS cells. Furthermore, activation of the Wnt/ß-catenin signaling pathway increased Sox4 expression levels through a positive feedback loop. These results suggested that CHMpCIS cells circumvented the damage caused by cisplatin through altering the expression of the Sox4 gene and activating the Wnt/ß-catenin pathway, thereby changing the cellular biological characteristics.

Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer.

BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.

Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of 3-month leuprorelin acetate (3-month LA, 11.25 mg) for the treatment of idiopathic central precocious puberty (ICPP) in Chinese girls. METHODS: We conducted a single-center retrospective study in China on 28 girls with ICPP who received at least one year of 3-month LA treatment. Data from anthropometry, biochemistry, bone age (BA), and pelvic ultrasonography were assessed before and every 6 months during medication. RESULTS: At CPP diagnosis, the mean chronological age (CA) was 7.8±0.8 years, with bone age advancement (BA-CA) of 1.5±0.8 years. After treatment initiation, growth velocity decreased significantly from 8.5±1.6 cm/year to 5.8±1.1 cm/year at month 12 (p<0.001). GnRH-stimulated peak LH ≤3IU/L, the primary efficacy criterion, was observed in 27 out of 28 (96.4 %) children at month 3. Basal estradiol <20 pg/mL was achieved by all 28 girls (100 %) at month 6 and remained stable at month 12. Basal follicle-stimulating hormone (FSH) decreased from 4.1±3.5 to 1.7±0.9 (p<0.001), and basal LH was also significantly reduced from 3.3±6.5 to 0.7±0.8 (p=0.035) at month 12. The mean predicted adult height (PAH) at treatment initiation was 152.7±5.8 cm, it increased significantly to 157.5±5.5 cm (p=0.007) after one-year treatment. Pubertal development was slowed in most patients, and in some cases, it was even reversed. Only one patient (3.6 %) reported local intolerance. CONCLUSIONS: Three-month leuprorelin acetate is a safe and effective treatment for suppressing the pituitary-gonadal axis and restoring impaired adult height in Chinese girls.

Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth.

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

Mechanism underlying the effect of Pulsatilla decoction in hepatocellular carcinoma treatment: a network pharmacology and in vitro analysis.

BACKGROUND: Currently, hepatocellular carcinoma (HCC) is associated with a poor prognosis. Moreover, there exist limited strategies for treating HCC. Pulsatilla decoction (PD), a traditional Chinese medicine formula, has been used to treat inflammatory bowel disease and several cancer types. Accordingly, we explored the mechanism of PD in HCC treatment via network pharmacology and in vitro experiments. METHODS: Online databases were searched for gene data, active components, and potential target genes associated with HCC development. Subsequently, bioinformatics analysis was performed using protein-protein interaction and Network Construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) to screen for potential anticancer components and therapeutic targets of PD. Finally, the effect of PD on HCC was further verified by in vitro experiments. RESULTS: Network pharmacological analysis revealed that 65 compounds and 180 possible target genes were associated with the effect of PD on HCC. These included PI3K, AKT, NF-κB, FOS, and NFKBIA. KEGG analysis demonstrated that PD exerted its effect on HCC mainly via the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments revealed that PD could significantly inhibit cancer cell proliferation and kill HCC cells by inducing apoptosis. Furthermore, western blotting confirmed that apoptosis was mediated primarily via the PI3K-AKT, IL-17, and TNF signaling pathways. CONCLUSION: To the best of our knowledge, this is the first study to elucidate the molecular mechanism and potential targets of PD in the treatment of HCC using network pharmacology.

Phytochemical content and antioxidant activity of different anatomical parts of Corchorus olitorius and C. capsularis during different phenological stages.

Different parts of Corchorus olitorius and C. capsularis possess different antioxidant compounds. This study investigated the phytochemical components and antioxidant capacities of ultrasound-assisted extraction of different plant parts of both species using spectrophotometry at various phenological stages. Results also indicate that leaves, stems and roots of C. olitorius at various growth stages showed higher phytochemical components and antioxidant potential compared to C. capsularis. The phytochemical components from roots to leaves in C. olitorius including total polyphenol 0.97-11.11 mg GAE/g DW, total flavonoid 0.99-7.78 mg QE/g DW and total tannin 4.02-26.89 TA E/g DW, whereas C. capsularis total polyphenol 1.04-7.93 mg GAE/g DW, total flavonoid 0.77-5.5.92 mg QE/g DW and total tannin content 3.17-22.73 TA E/g DW. C. olitorius produced overall 22.23%, 13.61%, 12.24% higher total polyphenol, total flavonoid and total tannin, respectively compare to C. capsularis. Different parts extract also significantly affected antioxidant capacities including DPPH, ABTS, and FRAP activity with values of 22.03-79.46% inhibition, 10.84-104.10 µmol TE/g DW, and 10.84-104.10 µmol Fe2+/g DW respectively for C. olitorius, while C. capsularis demonstrated 14.03-70.97% of DPPH inhibition, 9.16-95.60 µmol TE/g DW of ABTS and 5.31-71.82 µmol Fe2+/g DW of FRAP activity. Moreover, leaves of the flowering stage, young stems and aged roots of both species displayed a higher content of phytochemical and antioxidant activities than other growth stages. A positive correlation between the phytochemical and antioxidant potential indicated that phenolic constituents solely affected antioxidant activity. Thus, this study established that the plant's parts and phenological growth stages significantly influence the concentration of phytoconstituents and antioxidant activities, and determine the harvesting stages of the different organs of C. olitorius and C. capsularis for considerable medicinal importance as folk and industry.

Determining the mechanism of pulsatilla decoction for treating gastric cancer: a network pharmacology-based study.

Background and aim: Gastric cancer (GC) is a prevalent malignancy worldwide. Pulsatilla decoction (PD), a traditional Chinese medicine formula, can treat inflammatory bowel disease and cancers. In this study, we explored the bioactive components, potential targets, and molecular mechanisms of PD in the treatment of GC. Methods: We conducted a thorough search of online databases to gather gene data, active components, and potential target genes associated with the development of GC. Subsequently, we conducted bioinformatics analysis utilizing protein-protein interaction (PPI), network construction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify potential anticancer components and therapeutic targets of PD. Finally, the efficacy of PD in treating GC was further validated through in vitro experiments. Results: Network pharmacological analysis identified 346 compounds and 180 potential target genes associated with the impact of PD on GC. The inhibitory effect of PD on GC may be mediated through modulation of key targets such as PI3K, AKT, NF-κB, FOS, NFKBIA, and others. KEGG analysis showed that PD mainly exerted its effect on GC through the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments showed that PD could significantly inhibit proliferation and kill GC cells. Moreover, PD primarily induces apoptosis in GC cells. Western blotting analysis confirmed that the PI3K-AKT, IL-17, and TNF signaling pathways are the main mechanisms by which PD exerts its cytotoxic effects on GC cells. Conclusion: We have validated the molecular mechanism and potential therapeutic targets of PD in treating GC through network pharmacological analysis, thereby demonstrating its anticancer efficacy against GC.

Aplasia Cutis Congenita With Cutaneous Meningioma: A Rare Case.

ABSTRACT: Cutaneous meningioma, characterized by ectopic meningothelial cells in the dermis or subcutis, is a rare neoplasm. Generally, the most common location for cutaneous meningioma is the scalp. We report a case of cutaneous meningioma presenting as soft, light red, atrophic, and smooth patches with central blue spots. On histological examination, the tumor consisted largely of epithelioid cells, whorls, nests, and syncytial sheets of meningothelial cells. HMB-45, Melan-A, and S100 were negative; epithelial membrane antigen and somatostatin receptor 2 were positive. Ultimately, histopathologic examination and immunohistochemistry results supported a diagnosis of cutaneous meningioma. In addition, dermal dysplasia was observed above the tumor, manifested by thinning of the dermis and loss of appendages. No abnormalities were found on brain magnetic resonance imaging. Cutaneous meningioma is an extremely rare tumor, and its manifestation as an atrophic patch is even rarer. There have been mainly clinical reports of cutaneous meningioma. This was a rare case of focal aplasia cutis congenita with cutaneous meningioma. For cutaneous meningioma to be diagnosed earlier, there needs to be greater public awareness about the condition.

Vitamin D3 attenuates cisplatin-induced intestinal injury by inhibiting ferroptosis, oxidative stress, and ROS-mediated excessive mitochondrial fission.

Intestinal injury is one of the main side-effects of cisplatin (CP) chemotherapy, severely limiting the clinical application of CP. Vitamin D3 is an essential nutrient for mammals and exists in a wide range of foods; it regulates immune function and reduces oxidative stress. However, the effect of vitamin D3 on CP-induced intestinal injury is not elucidated. This is the first study to investigate the relationship between ferroptosis and the protective effect of vitamin D3 on CP-induced intestinal injury. An animal model of CP-induced intestinal injury was established to evaluate the effect of vitamin D3 on CP-induced intestinal injury and elucidate the underlying mechanisms. We found that vitamin D3 alleviated intestinal barrier injury and the abnormal morphological structure in CP-induced intestinal injury mice. Vitamin D3 suppressed oxidative stress by increasing the antioxidant capacity, inhibiting the accumulation of ROS and MDA, and reducing intestinal inflammatory responses. Vitamin D3 also decreased excessive mitochondrial fission and increased mitochondrial ATPase activity by inhibiting ROS production, which further alleviated the accumulation of ROS. We also confirmed the involvement of ferroptosis in CP-induced intestinal injury in our animal model using ferrostatin-1 (Fer-1) intervention. Vitamin D3 decreased iron accumulation and reversed GPX4 and DHODH down-regulation. In conclusion, vitamin D3 protected against CP-induced intestinal injury by inhibiting ferroptosis and alleviating oxidative stress and ROS-mediated excessive mitochondrial fission, suggesting that it may be a novel and promising candidate to prevent CP-induced intestinal injury.

Proanthocyanidins Alleviate Cadmium Stress in Industrial Hemp (Cannabis sativa L.).

Industrial hemp (Cannabis sativa L.), an annual herbaceous cash crop, is widely used for the remediation of heavy metal-contaminated soils due to its short growth cycle, high tolerance, high biomass, and lack of susceptibility to transfer heavy metals into the human food chain. In this study, a significant increase in proanthocyanidins was found in Yunnan hemp no. 1 after cadmium stress. Proanthocyanidins are presumed to be a key secondary metabolite for cadmium stress mitigation. Therefore, to investigate the effect of proanthocyanidins on industrial hemp under cadmium stress, four experimental treatments were set up: normal environment, cadmium stress, proanthocyanidin treatment, and cadmium stress after pretreatment with proanthocyanidins. The phenotypes from the different treatments were compared. The experimental results showed that pretreatment with proanthocyanidins significantly alleviated cadmium toxicity in industrial hemp. The transcriptome and metabolome of industrial hemp were evaluated in the different treatments. Proanthocyanidin treatment and cadmium stress in industrial hemp mainly affected gene expression in metabolic pathways associated with glutathione metabolism, phenylpropanoids, and photosynthesis, which in turn altered the metabolite content in metabolic pathways of phenylalanine, vitamin metabolism, and carotenoid synthesis. The combined transcriptomic and metabolomic analysis revealed that proanthocyanidins mitigated cadmium toxicity by enhancing photosynthesis, secondary metabolite synthesis, and antioxidant synthesis. In addition, exogenous proanthocyanidins and cadmium ions acted simultaneously on EDS1 to induce the production of large amounts of salicylic acid in the plant. Finally, overexpression of CsANR and CsLAR, key genes for proanthocyanidins synthesis in industrial hemp, was established in Arabidopsis plants. The corresponding plants were subjected to cadmium stress, and the results showed that CsLAR transgenic plants were more tolerant to cadmium than the CsANR transgenic and wild-type Arabidopsis plants. The results showed that salicylic acid and jasmonic acid were increased in Arabidopsis overexpressing CsLAR compared to AT wild-type Arabidopsis, and levels of secondary metabolites were significantly higher in Arabidopsis overexpressing CsLAR than in AT wild-type Arabidopsis. These results revealed how proanthocyanidins alleviated cadmium stress and laid the foundation for breeding industrial hemp varieties with higher levels of proanthocyanidins and greater tolerance.

Fluorescence recovery based on synergetic effect for ALP detection.

Alkaline phosphatase (ALP) is an important biomarker associated with diabetes, liver dysfunction, bone diseases, and breast cancer. Here we developed a method based on synergetic fluorescence recovery for the sensitive detection of ALP. Cadmium-zinc-selenium (CdZnSe) quantum dots (QDs) were prepared by one-pot water bath method without any complicated and rigorous conditions. CdZnSe QDs displayed high luminous efficiency, good stability, and good biocompatibility. KMnO4 and ascorbic acid phosphate (AAP) can dynamically quench the fluorescence of CdZnSe QDs. Ascorbic acid, produced by ALP-catalyzed hydrolysis of AAP, reacted with KMnO4, causing the synergetic fluorescence recovery of CdZnSe QDs. The synergetic recovery efficiency correlates well with the logarithmic ALP concentration in the range of 2.5-250 U/L with a detection limit of 0.21 U/L. In addition, good recoveries were obtained in the detection of ALP in human serum. This method provided a new research idea to improve the detection sensitivity and selectivity of ALP detection.

Troxerutin alleviates kidney injury in rats via PI3K/AKT pathway by enhancing MAP4 expression.

Background: Troxerutin is a flavonoid compound and possesses potential anti-cancer, antioxidant, and anti-inflammatory activities. Besides, cisplatin is one of the most widely used therapeutic agents, but the clinical uses of cisplatin are often associated with multiple side effects, among which nephrotoxicity is more common. Objective and design: This study explored the protective effects of troxerutin (150 mg kg-1 day-1 for 14 days) against cisplatin-induced kidney injury and the potential mechanism using Wistar rats as an experimental mammalian model. Results: We discovered that troxerutin could significantly alleviate cisplatin-induced renal dysfunction, such as increased levels of blood urea nitrogen and creatinine (P < 0.01), as well as improved abnormal renal tissue microstructure and ultrastructure. Additionally, troxerutin significantly decreased malondialdehyde (MDA), hydrogen peroxide (H2O2), NO, inducible nitric oxide synthase (iNOS) levels (P < 0.01), p-NF-κB p65/NF-κB p65, TNF-α, Pro-IL-1ß, IL-6, B cell lymphoma-2 (Bcl-2)/Bcl-xl associated death promoter (Bad), Cytochrome C (Cyt C), Cleaved-caspase 9, Cleaved-caspase 3, and Cleaved-caspase 8 protein levels (P < 0.01) in the kidney tissues of cisplatin-treated rats; and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total antioxidant capacity (T-AOC) activities (P < 0.01), IL-10, Bcl-2 protein levels (P < 0.01). Conclusion: These results suggested that the underlying mechanism might be attributed to the regulation of Phosphoinositide 3 kinase/Protein kinase B (PI3K/AKT) pathway via enhancing MAP4 expression to attenuate cellular apoptosis, alleviating oxidative stress and inflammatory response.

A Comprehensive Review of C. capsularis and C. olitorius: A Source of Nutrition, Essential Phytoconstituents and Pharmacological Activities.

Plant bioactive compounds have gained global significance in terms of both medicinal and economic ramifications due to being easily accessible and are believed to be effective with fewer side effects. Growing relevant clinical and scientific evidence has become an important criterion for accepting traditional health claims of medicinal plants and also supports the traditional uses of Corchorus as folk medicine. C. capsularis and C. olitorius have broad applications ranging from textile to biocomposite, and young leaves and shoots are used as healthy vegetables and have long been used as traditional remedies for fever, ascites, algesia, liver disorders, piles, and tumors in many cultures. This review systematically summarized and emphasized the nutritional attributes, mostly available bioactive compounds, and biological and potential pharmaceutical properties of C. capsularis and C. olitorius, disclosed to users and non-users. Results suggest that various phytochemicals such as cardiac glycosides, phenols, flavonoids, sterols, lipids, and fatty acids were found or analytically identified in different plant parts (leaf, stem, seed, and root), and many of them are responsible for pharmacological properties and their antitumor, anticancer, antioxidant, antinociceptive, anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticonvulsant, antidiabetic and antiobesity, and cardiovascular properties help to prevent and cure many chronic diseases. In addition to their use in traditional food and medicine, their leaves have also been developed for skin care products, and some other possible uses are described. From this review, it is clear that the isolated compounds of both species have great potential to prevent and treat various diseases and be used as functional foods. In conclusion, this comprehensive review establishes a significant reference base for future research into various medical and functional food applications.

Dioscin Alleviates Cisplatin-Induced Mucositis in Rats by Modulating Gut Microbiota, Enhancing Intestinal Barrier Function and Attenuating TLR4/NF-κB Signaling Cascade.

Cisplatin-based chemotherapy causes intestinal mucositis, which causes patients immense suffering and hinders the process of cancer treatment. Dioscin is a natural steroid saponin that exhibits strong anti-inflammatory and immunomodulatory properties. Herein, we investigate the protective effect of dioscin on cisplatin induced mucositis in rats from the perspective of gut microbiota and intestinal barrier. We established a rat model of intestinal mucositis by tail vein injection of cisplatin, and concurrently treated with dioscin oral administration. Parameters, such as body weight, diarrheal incidence, and D-Lactate levels, were assessed in order to evaluate the effects of dioscin on intestinal mucositis in rats. Furthermore, biological samples were collected for microscopic gut microbiota, intestinal integrity, and immune inflammation analyses to elucidate the protective mechanisms of dioscin on intestinal mucositis. The results revealed that administration of dioscin significantly attenuated clinical manifestations, histological injury and inflammation in mucositis rats. Besides this, dioscin markedly inhibited the gut microbiota dysbiosis induced by cisplatin. Meanwhile, dioscin partially alleviated junctions between ileum epithelial cells and increased mucus secretion. Moreover, dioscin effectively inhibited the TLR4-MyD88-NF-κB signal transduction pathway and reduced the secretion of subsequent inflammatory mediators. These results suggested that dioscin effectively attenuated cisplatin-induced mucositis in part by modulating the gut microflora profile, maintaining ileum integrity and inhibiting the inflammatory response through the TLR4-MyD88-NF-κB pathway.

Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt/ß-catenin-TFE3 feedback loop signalling.

BACKGROUND: Ferroptosis is principally caused by iron catalytic activity and intracellular lipid peroxidation. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the potential interplay between lncRNA LINC01606 and ferroptosis in colon cancer remains elusive. METHODS: The expression level of LNC01606 in colon cancer tissue was detected by quantitative real-time polymerase chain reaction. The functional role of LNC01606 was investigated by gain- and loss-of-function assays both in vitro and in vivo. The LINC01606-SCD1-Wnt/ß-catenin-TFE3 axis were screened and validated by DNA/RNA pull down, gas chromatography-mass spectrometry, RNA immunoprecipitation and dual-luciferase reporter. RESULTS: The expression of lncRNA LINC01606 was frequently upregulated in human colon cancer and strongly associated with a poor prognosis. LINC01606 functioned as an oncogene and promotes colon cancer cell growth, invasion and stemness both in vitro and in vivo. Moreover, LINC01606 protected colon cancer cells from ferroptosis by decreasing the concentration of iron, lipid reactive oxygen species, mitochondrial superoxide and increasing mitochondrial membrane potential. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/ß-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. Furthermore, we confirmed that upregulated LINC01606 and Wnt/ß-catenin formed a positive feedback regulatory loop, further inhibiting ferroptosis and enhancing stemness. CONCLUSIONS: LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer.

Indicators of glucose dysregulation and the relationship with iron overload in Chinese children with beta thalassemia major.

INTRODUCTION: Patients with beta thalassemia major (TM) have a higher risk of diabetes and an abnormal oral glucose tolerance test (OGTT), but there is no single agree monitoring parameter that reflects glycemic status. The possible mechanisms include iron overload and blood transfusion, but they require further investigation. PURPOSE: This study explored the role of glycated hemoglobin A1c (HbA1c), fructosamine, and glycated albumin (GA) in evaluating the glucose dysregulation and to determine the potential relationship between iron deposition and glucose metabolism disorder in beta TM. METHODS: A cross-sectional study was performed on 118 patients with beta TM and the control group consisted of 33 healthy children with no statistical differences in age, sex, and body mass index (BMI). Fast plasma glucose (FPG), fast insulin (FINS), insulin resistance index (HOMA-IRI), and insulin sensitivity index (HOMA-ISI) were compared between the patient and control groups. HbA1c, GA, fructosamine, and serum ferritin (SF) were measured in the patient group. OGTT, as well as heart and liver magnetic resonance imaging (MRI) T2*, was performed. For all statistical analyses, SPSS 21.0 was used and p < 0.05 was accepted as statistically significant. RESULTS: FPG, FINS, and HOMA-IRI were significantly increased while HOMA-ISI decreased in the beta TM patients when compared with those in the control group. In patients with beta TM, 17 (14.41%) of patients had been diagnosed with diabetes, while 48 (40.68%) had both impaired fasting glucose and impaired glucose tolerance. HbA1c, GA, and fructosamine were increased according to the degree of abnormal glucose metabolism. Statistically significant differences were found in age, SF, and cardiac T2* between the abnormal and normal OGTT groups. CONCLUSION: HbA1c may be used as a significant measure for monitoring glycemic levels in patients with beta TM. Furthermore, GA and fructosamine were alternative indicators of glucose status. Patients with heart iron deposition or an SF > 4000 µg/L were prone to abnormal glucose metabolism, so chelation therapy should be reinforced.

Combined supplementation of sodium humate and glutamine reduced diarrhea incidence of weaned calves by intestinal microbiota and metabolites changes.

This study was conducted to investigate the effects of combined supplementation of sodium humate (HNa) and glutamine (Gln) on growth performance, diarrhea incidence, serum parameters, intestinal microbiome, and metabolites of weaned calves. In Exp. 1, 40 calves were randomly assigned to four treatments: 1) NC (negative control, basal diet), 2) 1% H+1% G (basal diet extra orally gavaged with 1 g of HNa and 1 g of Gln daily), 3) 3% H+1% G (basal diet extra orally gavaged with 3 g of HNa and 1 g of Gln daily), and 4) 5% H+1% G (basal diet extra orally gavaged with 5 g of HNa and 1 g of Gln daily). The HNa and Gln were together mixed with 100 mL of milk replacer (51 to 58 d of age) or water (59 to 72 d of age) and orally administrated to each calf from a bottle before morning feeding. In a 21-d trial, calves on the 5% HNa+1% Gln group had higher (P < 0.05) average daily gain (ADG) and lower (P < 0.05) diarrhea incidence than those in the control group. In Exp. 2, 20 calves were randomly assigned to two treatments fed with a basal diet and a basal diet supplemented with 100 mL of 5% HNa+1% Gln. In a 21-d trial, calves supplemented with HNa and Gln had higher (P < 0.05) ADG, IgG concentration and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) activities in the serum, but lower (P < 0.05) diarrhea incidence, as well as serum diamine oxidase (DAO), D-isomer of lactic acid (D-lac), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) concentrations compared with control group. Results of intestinal microbiota indicated that supplementation with HNa and Gln significantly increased (P < 0.05) the abundance of intestinal beneficial microbiota. Moreover, supplementation with HNa and Gln altered 18 metabolites and enriched 6 Kyoto Encyclopedia of Genes and Genomes pathways in weaned calves. In conclusion, combined supplementation with HNa and Gln could decrease diarrhea incidence of weaned calves via altering intestinal microbial ecology and metabolism profile.