Black raspberry-mediated metabolic changes in patients with familial adenomatous polyposis associated with rectal polyp regression.

Familial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, while the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry-based non-targeted metabolomics, we analyzed pre- and post-BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post-BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.

Application of exosomes in tumor immunity: recent progresses.

Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.

Collagen-EGCG Combination Synergistically Prevents UVB-Induced Skin Photoaging in Nude Mice.

Ultraviolet (UV) radiation is a major cause of skin photoaging through generating excessive oxidative stress and inflammation. One of the strategies is to use photo-chemoprotectors, such as natural products with antioxidant and anti-inflammatory properties, to protect the skin from photo damage. The present study investigates the photoprotective potentials of topical administration of unhydrolyzed collagen, epigallocatechin gallate (EGCG), and their combination against ultraviolet B (UVB)-induced photoaging in nude mice. It is found that both the solo and combined pretreatments could recover UVB-induced depletion of antioxidative enzymes, including superoxide dismutase and glutathione peroxidase (GSH-Px), as well as an increase of lipid peroxide malondialdehyde and inflammatory tumor necrosis factor-α. Meanwhile, the UVB-stimulated skin collagen degradation is attenuated significantly with drug treatments, which is evidenced by expression analysis of matrix metalloproteinase-1 and hydroxyproline. Additionally, the mouse skin histology shows that the drug-pretreated groups possess decreased epidermis thickness and normal collagen fiber structure of the dermis layer. These results demonstrate that both EGCG and collagen can protect the skin against UVB-induced skin photoaging. Synergistically, the combination of them shows the maximum prevention to skin damage, showing its potential in the application of anti-photoaging formulation products.

Metallic phase enabling MoS2 nanosheets as an efficient sonosensitizer for photothermal-enhanced sonodynamic antibacterial therapy.

Two-dimensional (2D) transition metal dichalcogenide (TMD) nanosheets (e.g., MoS2) with metallic phase (1T or 1T´ phase) have been proven to exhibit superior performances in various applications as compared to their semiconducting 2H-phase counterparts. However, it remains unclear how the crystal phase of 2D TMD nanosheets affects their sonodynamic property. In this work, we report the preparation of MoS2 nanosheets with different phases (metallic 1T/1T´ or semiconducting 2H) and exploration of its crystal-phase effect on photothermal-enhanced sonodynamic antibacterial therapy. Interestingly, the defective 2D MoS2 nanosheets with high-percentage metallic 1T/1T´ phase (denoted as M-MoS2) present much higher activity towards the ultrasound-induced generation of reactive oxygen species (ROS) as compared to the semiconducting 2H-phase MoS2 nanosheets. More interestingly, owing to its metallic phase-enabled strong absorption in the near-infrared-II (NIR-II) regime, the ultrasound-induced ROS generation performance of the M-MoS2 nanosheets can be further enhanced by the photothermal effect under a 1064 nm laser irradiation. Thus, after modifying with polyvinylpyrrolidone, the M-MoS2 nanosheets can be used as an efficient sonosensitizer for photothermal-enhanced sonodynamic bacterial elimination under ultrasound treatment combining with NIR-II laser irradiation. This study demonstrates that metallic MoS2 nanosheets can be used as a promising sonosensitizer for antibacterial therapy, which might be also promising for cancer therapies.

Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework.

Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D) in-vitro culture models of tumorigenesis are inadequate to replicate the complexity of in-vivo microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.

Expression of kindlin-3 in melanoma cells impedes cell migration and metastasis.

Kindlins are a small family of 4.1-ezrin-radixin-moesin (FERM)-containing cytoplasmic proteins. Kindlin-3 is expressed in platelets, hematopoietic cells, and endothelial cells. Kindlin-3 promotes integrin activation, clustering and outside-in signaling. Aberrant expression of kindlin-3 was reported in melanoma and breast cancer. Intriguingly, kindlin-3 has been reported to either positively or negatively regulate cancer cell metastasis. In this study, we sought to clarify the expression of kindlin-3 in melanoma cells and its role in melanoma metastasis. Two widely used metastatic mouse and human melanoma cell lines B16-F10 and M10, respectively, were examined and found to lack kindlin-3 mRNA and protein expression. When kindlin-3 was ectopically expressed in these cells, cell migration was markedly reduced. These are attributed to aberrant Rac1 and RhoA activation and overt membrane ruffling. Our data demonstrate for the first time that despite its well established role as a positive regulator of integrin-mediated cell adhesion, aberrant expression of kindlin-3 could lead to imbalanced RhoGTPases signaling that impedes rather than promotes cell migration.

Study on effect of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema.

OBJECTIVE: To study the effects of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema. METHODS: DNCB acetone solution was used to sensitize the skin of back and ears of 36 rats in order to establish chronic eczema model. A total of 36 rats were divided into four groups of 9 randomly including oral medicine group, external inunctum group, combination therapy group, and model control group respectively. Besides, the blank group of 4 healthy rats were set. The oral medicine group was given Traditional Chinese Medicine Jianpi Chushi decoction [(Poria cocos, Chinese yam, Cortex dictamni, Zaocys dhumnade, Rhizoma atractylodis, Pericarpium citri reticulatae, Scutellaria baicalensis, Radix Sophorae Flavescentis, Raw Radix Paeoniae Alba, Licorice roots (Northwest Origin)] by gastric infusion (1.6 g/mL·5 mL/d); the external inunctum group was given Qingpeng ointment on the skin, the combination therapy group was given Jianpi Chushi decoction by gastric infusion and Qingpeng ointment combination therapy. The model control group was given normal saline (NS) of the same volume by gastric infusion and vaseline on skin. Continuous administration 15 d and stopped for 3 d. The thickness difference and weight difference of left and right ear of every group were measured and the degree of ear swelling were evaluated. The CD4+ and CD8+ content and the IL-2, IL-4 level of serum were detected, and the inflammatory cells counts of back skin were recorded. RESULTS: After treatment, the degree of ear swelling of oral medicine group, external inunctum group and combination therapy group significant decreased compared with model control group (P < 0.05). The CD4+, CD8+ cell content and IL-2 level of oral medicine group, external inunctum group, combination therapy group and model control group significant decreased compared with blank group, and IL-2 level and the inflammatory cells count increased. After 15 d of treatment, the CD4+, CD8+ cell content and IL-2 level of serum of oral medicine group, external inunctum group and combination therapy group raised and the IL-4 level and the inflammatory cells count had significant decreased compared with model control group, and the effect of combination therapy group was more obvious (P < 0.05). CONCLUSIONS: Qral Jianpi Chushi decoction could treat chronic eczema effectively, and oral Chinese medicine combined with ointment could enhance and speed up the efficacy.

Micropatterning Extracellular Matrix Proteins on Electrospun Fibrous Substrate Promote Human Mesenchymal Stem Cell Differentiation Toward Neurogenic Lineage.

In this study, hybrid micropatterned grafts constructed via a combination of microcontact printing and electrospinning techniques process were utilized to investigate the influencing of patterning directions on human mesenchymal stem cells (hMSCs) differentiation to desired phenotypes. We found that the stem cells could align and elongate along the direction of the micropattern, where they randomly distributed on nonmicropatterned surfaces. Concomitant with patterning effect of component on stem cell alignment, a commensurate increase on the expression of neural lineage commitment markers, such as microtubule associated protein 2 (MAP2), Nestin, NeuroD1, and Class III ß-Tubulin, were revealed from mRNA expression by quantitative Real Time PCR (qRT-PCR) and MAP2 expression by immunostaining. In addition, the effect of electrospun fiber orientation on cell behaviors was further examined. An angle of 45° between the direction of micropatterning and orientation of aligned fibers was verified to greatly prompt the outgrowth of filopodia and neurogenesis of hMSCs. This study demonstrates that the significance of hybrid components and electrospun fiber alignment in modulating cellular behavior and neurogenic lineage commitment of hMSCs, suggesting promising application of porous scaffolds with smart component and topography engineering in clinical regenerative medicine.

A new member of the DMATS superfamily from Aspergillus niger catalyzes prenylations of both tyrosine and tryptophan derivatives.

A putative prenyltransferase gene of the dimethylallyltryptophan synthase (DMATS) family, An13g01840, was identified in the genome sequence of Aspergillus niger. The deduced polypeptide CAK41583 consists of 465 amino acids with a calculated molecular mass of 52.7 kDa. To evaluate gene function, the coding sequence was cloned into pET28a and overexpressed in Escherichia coli. The soluble His6-fusion protein was purified to near homogeneity on Ni-NTA agarose and used for enzyme assays with diverse aromatic substrates in the presence of dimethylallyl diphosphate. HPLC analysis revealed product formation in the incubation mixtures with L-tyrosine and five derivatives thereof. Structure elucidation of the enzyme products by NMR and MS analyses confirmed O-prenylations and proved the identification of a tyrosine O-prenyltransferase (TyrPT). As in the case of SirD from Leptosphaeria maculans, TyrPT also accepted 4-amino-L-phenylalanine for an N-prenylation and L-tryptophan for a C7-prenylation. The K M values of TyrPT for L-tyrosine, L-tryptophan, and dimethylallyl diphosphate (DMAPP) were found to be 0.24, 0.19, and 0.71 mM, respectively. The k cat of L-tyrosine and L-tryptophan reactions were determined at 0.58 and 0.0053 s(-1), respectively. The results presented in this study enhance the relationship of tyrosine O- and tryptophan C7-prenyltranferases and provide meanwhile a new enzyme for production of prenylated derivatives. In comparison to the known tyrosine prenyltransferase SirD, TyrPT showed significantly higher catalytic activity for several substrates, e.g., 4-amino-L-phenylalanine as well as 4- and 5-methyl-DL-tryptophan.

[Anticancer effect of hydroxycampothecin on oral squamous carcinoma cell line].

BACKGROUND & OBJECTIVE: Studies have demonstrated that hydroxycamptothecin (HCPT) had therapeutic effect on many malignant tumors, but few studies on oral squamous cell carcinoma were reported. This study was designed to investigate the anticancer effect and mechanism of hydroxycampothecin (HCPT) on oral squamous carcinoma cell line (Tca8113). METHODS: The cytotoxicity of HCPT on Tca8113 cell line was measured by MTT assay and cell cycle detected by flow cytometry(FCM). The growth status of Tca8113 cell xenografts following treatment with HCPT was observed. The doubling times and tumor inhibition rate were calculated. RESULTS: HCPT had strong cytotoxicity on Tca8113 cells, the IC50 was 2 mumol/L. After treatment with low concentration of HCPT, the cell cycle was arrested in S phase or G2 + M phase; while at high concentration, apoptosis was obviously found and the rate of apoptosis was increased as the time and concentration of HCPT. Compared with control group, the xenografts of HCPT treated group grew slower and tumor doubling time was prolonged, The tumor volumes of HCPT treated group at 28th day were significantly smaller(P < 0.001) with tumor inhibition rate of 69.6%. CONCLUSION: The result showed that HCPT had strong cytotoxicity effect to oral squamous carcinoma cells and significant growth inhibition on Tca8113 xenografts. HCPT can arrest cell cycle in S phase and G2 + M phase and induce cell apoptosis.