Tumor Growth Factor Beta Research Articles

Host cytokine genetic polymorphisms in a selected population of persons living with hepatitis B virus infection in the central region of Ghana.

Hepatitis B virus (HBV) infection is a public health concern in resource limited settings like Ghana. Over the past decades, it is noted that the natural course of HBV in persons infected are taking a worse turn leading to liver cirrhosis and cancer. The outcome of HBV infection is influenced by viral and host factors including genetics. Cytokine variations affect virus survival and progression and may even influence associated complications. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (IL-4, IL-6, IL-8, IL-10, IL-18), interferon gamma (IFN)-γ, and tumor growth factor-beta (TGF-β) have key roles in HBV infection and modulation. In this study, polymorphisms occurring in five cytokines were analysed to understand how they can influence prognosis of HBV infection. The study is a single centre cross-sectional study involving 227 participants made up of HBV infected participants and HBV-negative controls. Recruitment was from March 2021 to April 2022. Blood samples were taken for full blood count, HBV antigen profile, liver function tests, HBV DNA quantification and cytokine genotyping. FIB score was calculated using available tools. Statistical analysis was undertaken with p < 0.05 set as statistically significant. The 20-39-year-old group formed majority of the HBV infected participants with 60% of all participants being classified as healthy HBsAg carriers. IL2 rs1479920 GG carriers ((1258.93; 0.00-5011.87) IU/mL had reduced HBV DNA in comparison to IL2 rs1479920 AA ((5011.87; 2113.49-5956.62) /AG (3548.13; 0.00-6309.57) IU/mL carriers. TNF-α rs1800629 AA carriers (1258.93; 0.00-3981.07) IU/mL had a reduction in HBV DNA levels in comparison to TNF-α rs1800629 GG carriers (1584.89; 0.00-5011.87) IU/mL. The results of univariate (OR = 0.08, 0.00-0.93; p = 0.043) and multivariate (OR = 0.02, 0.00-0.67; p = 0.029) analysis, showed that carrying TNF-α rs1800629 AA genotype reduce susceptibility to high FIB score compared with GG genotypes. In univariate analysis, subjects aged 20-39years (OR = 5.00, 1.13-6.10; p = 0.034) and 40-59years (OR = 41.99, 3.74-47.21; p = 0.0002) were more susceptible to high FIB score compared to subjects aged 1-19years. Being female (OR = 2.42, 1.03-5.71; p = 0.043) in the univariate models showed higher odds of having high levels of HBV DNA in the multivariate model. There was a reduced likelihood of herbal medicine usage influencing HBV DNA levels significantly (OR = 0.29, 0.10-0.86; p = 0.025). In conclusion, variations in IL2 rs1479920 GG and IL2 rs1479921 AA could offer protective effects by reducing HBV DNA. TNF-α rs179924CT may also cause elevation in HBV DNA levels whiles TNF-α -308A/G, showed a potential protective effect on liver scarring in HBV infected participants. It is therefore important to take a further look at such variations for understanding of HBV modulation in the Ghanaian population.

SARS-COV-2 CORONAVIRUS ANTIGENS MODULATE THE ACTIVITY OF HUMAN T-REGULATORY CELLS

Regulatory T cells (Treg cells) play a crucial role in regulation of immune response. It is believed that excessive activity of Treg cells in the early stages of infectious diseases reduces the pro-inflammatory activity of cells in the innate and adaptive immune response, thereby contributing to the development of chronic inflammation or excessive inflammation. Additionally, it is known that aging leads to changes in the quantity of Treg cells and disrupts their activity. It is established that infection with the SARS-CoV-2 virus leads to fatal and severe cases of the disease, primarily among the elderly population. However, the underlying cause of the development of severe forms in elderly individuals remains incompletely understood. Thus, we hypothesized that the dysregulation of the Treg cell activity in elderly individuals may contribute to the development of severe forms and lethality from SARS-CoV-2, leading to the emergence of hyper inflammation in this population. To investigate the impact of SARS-CoV-2 on the immunosuppressive properties of Treg cells, venous blood samples were obtained from young healthy volunteers and elderly individuals. Dendritic cells were obtained by PBMC adhesion on plastic. Adherent monocytes were cultured in cytokine medium with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-SCF), with addition of lipopolysaccharide (LPS) after 48 hours and incubated for an additional 24 hours with S1 or N antigens of SARS-CoV-2 virus. The obtained dendritic cells presenting SARS-CoV-2 antigens were then co-cultured with autologous CD4+-T lymphocytes ex vivo. The expression level of immunosuppressive membrane-associated and soluble molecules expressed by Treg cells was assessed using flow cytometry. Our results indicate that the immunosuppressive activity of Treg cells exhibits contrasting patterns in the two donor groups studied in response to the presentation of SARS-CoV-2 antigens. The proportion of Treg cells, as well as the expression levels of the immunosuppressive molecules, including tumor growth factor beta (TGF-b), CD39, glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein, and the levels of the intracellular immunosuppressive cytokines, including IL-10 and IL-35, in Treg cells obtained from peripheral blood of elderly donors, significantly increased in response to the presentation of SARS-CoV-2 antigens ex vivo, when compared to the group of young donors. Conversely, in the group of young donors were observed a decrease in the expression of these markers and an increase in the concentration of extracellular pro-inflammatory cytokines IL-2 and IFN-γ ex vivo, which activate the effector immune cells and contribute to virus elimination. In summary, the presented results suggest that Treg cells derived from elderly individuals exhibit elevated immunosuppressive activity in response to SARS-CoV-2 antigens ex vivo. Obtained results may indicate that in elderly individuals on the early stages of SARS-CoV-2 infection Treg cells may also possess enhanced immunosuppressive activity, which may contribute to the overall suppression of anti-viral immune responses, thereby potentially leading to the delayed SARS-CoV-2 virus clearance and development of severe forms of the disease.

The Anti-Atherosclerotic Effects of Buyang Huanwu Decoction through M1 and M2 Macrophage Polarization in an ApoE Knockout Mouse Model.

Arteriosclerosis (AS) is a chronic inflammatory disease and Buyang Huanwu decoction (BHD) has been identified as an anti-atherosclerosis effect, and the study is aimed to investigate the underlying mechanism. The E4 allele of Apolipoprotein E (ApoE) is associated with both metabolic dysfunction and an enhanced pro-inflammatory response, ApoE-knockout (ApoE-/-) mice were fed with a high-fat diet to establish an arteriosclerosis model and treated with BHD or atorvastatin (as a positive control). The atherosclerotic plaque in each mouse was evaluated using Oil red O Staining. Elisa kits were used to evaluate blood lipid, interleukin-6 (IL-6), IL-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), IL-4, IL-10, and tumor growth factor beta (TGF-β) contents, while Western blot was applicated to measure inducible nitric oxide synthase (iNOS), arginase I (Arg-1) expression. Meanwhile, pyruvate kinase M2 (PKM2), hypoxia-inducible factor-1 alpha (HIF-1α) and its target genes glucose transporter type 1 (GLUT1), lactate dehydrogenase A (LDHA), and 3-phosphoinositide-dependent kinase 1 (PDK1), as well as IL-6, IL-1β, TNF-α, IL-4, IL-10, and TGF-β were evaluated by the quantitative reverse transcription-polymerase chain reaction. BHD treatment significantly reduced body weight and arteriosclerosis plaque area and blood lipid levels including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Meanwhile, BHD demonstrated a significant suppression of M1 polarization, by decreased secretion of iNOS and pro-inflammatory factors (IL-6, IL-1β, and TNF-α) in ApoE-/- mice. The present study also revealed that BHD promotes the activation of M2 polarization, characterized by the expression of Arg-1 and anti-inflammatory factors (IL-4 and IL-10). In addition, PKM2/HIF-1α signaling was improved by M1/M2 macrophages polarization induced by BHD. The downstream target genes (GLUT1, LDHA, and PDK1) expression was significantly increased in high fat feeding ApoE-/- mice, and those of which were recused by BHD and Atorvastatin. These results suggested that M1/M2 macrophages polarization produce the inflammatory response against AS progress after BHD exposure.

TGF-β Isoforms and GDF-15 in the Development and Progression of Atherosclerosis.

The effect of oxidised lipoproteins on the endothelium, monocytes, platelets, and macrophages is a key factor in the initiation and development of atherosclerosis. Antioxidant action, lipoprotein metabolism, and chronic inflammation are the fields of research interest for better understanding the development of the disease. All the fields are related to inflammation and hence to the secretion of cytokines, which are being investigated as potential diagnostic markers for the onset of atherosclerosis. Pathways of vascular damage are crucial for the development of new laboratory readouts. The very early detection of endothelial cell damage associated with the onset of atherosclerosis, allowing the initiation of therapy, remains a major research goal. This article summarises the latest results on the relationship of tumour growth factor beta (TGF-β) isoforms and growth differentiation factor 15 (GDF-15) to the pathogenesis of atherosclerosis: which cells involved in atherosclerosis produce them, which effectors stimulate their synthesis and secretion, how they influence atherosclerosis development, and the relationship between the levels of TGF-β and GDF-15 in the blood and the development and extent of atherosclerosis.

Human archetypal pluripotent stem cells differentiate into trophoblast stem cells via endogenous BMP5/7 induction without transitioning through naive state

Primary human trophoblast stem cells (TSCs) and TSCs derived from human pluripotent stem cells (hPSCs) can potentially model placental processes in vitro. Yet, the pluripotent states and factors involved in the differentiation of hPSCs to TSCs remain poorly understood. In this study, we demonstrate that the primed pluripotent state can generate TSCs by activating pathways such as Epidermal Growth Factor (EGF) and Wingless-related integration site (WNT), and by suppressing tumor growth factor beta (TGFβ), histone deacetylases (HDAC), and Rho-associated protein kinase (ROCK) signaling pathways, all without the addition of exogenous Bone morphogenetic protein 4 (BMP4)—a condition we refer to as the TS condition. We characterized this process using temporal single-cell RNA sequencing to compare TS conditions with differentiation protocols involving BMP4 activation alone or BMP4 activation in conjunction with WNT inhibition. The TS condition consistently produced a stable, proliferative cell type that closely mimics first-trimester placental cytotrophoblasts, marked by the activation of endogenous retroviral genes and the absence of amnion expression. This was observed across multiple cell lines, including various primed induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines. Primed-derived TSCs can proliferate for over 30 passages and further specify into multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our research establishes that the differentiation of primed hPSCs to TSC under TS conditions triggers the induction of TMSB4X, BMP5/7, GATA3, and TFAP2A without progressing through a naive state. These findings propose that the primed hPSC state is part of a continuum of potency with the capacity to differentiate into TSCs through multiple routes.

Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway.

The role of Tousled-like kinase 1 (TLK1) in in gastric cancer (GC) remains unclear. To investigate the expression, biological function, and underlying mechanisms of TLK1 in GC. We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence, respectively. We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation, 5-ethynyl-2`-deoxyuridine, and Transwell assays as well as flow cytometry. We applied bioinformatics to elucidate the signaling pathways associated with TLK1. We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice. TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus. TLK1 knockdown significantly decreased colony formation, proliferation, invasion, and migration but increased apoptosis in GC cells. TLK1 overexpression had the opposite effects. Bioinformatics revealed, and subsequent experiments verified, that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression. The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC. The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is, therefore, promising as a therapeutic target against this disease.

Primary cilium participates in radiation-induced bystander effects through TGF-β1 signaling.

Many studies have indicated that tumor growth factor-beta (TGF-β) signaling mediates radiation-induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF-β signaling to regulate diverse cellular processes. But whether the PC participates in TGF-β induced RIBEs remains unclear.The cellular levels of TGF-β1 were detected by western blot analysis and the secretion of TGF-β1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining. G0 /G1 phase cells were arrested by serum starvation and S phase cells were induced by double thymidine block. The TGF-β1 signaling was interfered by LY2109761, a TGF-β receptor 1 (TβR1) inhibitor, or TGF-β1 neutral antibody. The DNA damages were induced by TGF-β1 or radiated conditional medium (RCM) from irradiated cells and were reflected by p21 expression, 53BP1 foci, and γH2AX foci.Compared with unirradiated control, both A549 and Beas-2B cells expressed and secreted more TGF-β1 after carbon ion beam or X-ray irradiation. RCM collected from irradiated cells or TGF-β1 treatment caused an increase of DNA damage in cocultured unirradiated Beas-2B cells while blockage of TGF-β signaling by TβR1 inhibitor or TGF-β1 neutral antibody alleviates this phenomenon. IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF-β1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G0 /G1 phase cells which showed higher PC formation rate.This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF-β1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs.

Nicotinic acid attenuates experimental non-alcoholic steatohepatitis by inhibiting the NLRP3 inflammasome/pyroptosis pathway

Non-alcoholic steatohepatitis (NASH) is a global public health concern that may progress into fibrosis, cirrhosis, and liver cancer, with limited curative treatment options. While the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is closely linked to NASH progression, nicotinic acid (NA), a vitamin used for the treatment of dyslipidemia, is an emerging pharmaceutical treatment for hepatic steatosis and fibrosis. Here, we investigated pharmacological effects of NA on experimental NASH and whether NLRP3 inflammasome/pyroptosis inhibition is an associated mechanism of action. Rats were fed a high-fat sucrose diet supplemented with cholesterol and a low dose of CCl4. NA significantly reduced inflammation by decreasing the protein levels of tumor necrosis factor-alpha and nuclear factor kappa B. Moreover, NA inhibited the formation of NLRP3- apoptosis-associated speck-like protein containing caspase recruitment domain-Caspase-1, decreasing interleukin-1beta, interleukin-18, and gasdermin D protein. In addition, NA reduced tumor growth factor-beta, alpha-smooth muscle actin, and hepatic levels of collagen-1, consequently decreasing extracellular matrix synthesis. Our results indicate that NA can inhibit NASH progression and encourage further basic and clinical studies on the use of NA for the treatment of human NASH.

African Swine Fever Virus Interaction with Host Innate Immune Factors.

African swine fever virus (ASFV) adversely affects pig farming owing to its 100% mortality rate. The condition is marked by elevated body temperature, bleeding, and ataxia in domestic pigs, whereas warthogs and ticks remain asymptomatic despite being natural reservoirs for the virus. Breeding ASFV-resistant pigs is a promising solution for eradicating this disease. ASFV employs several mechanisms to deplete the host antiviral response. This review explores the interaction of ASFV proteins with innate host immunity and the various types of machinery encompassed by viral proteins that inhibit and induce different signaling pathways, such as cGAS-STING, NF-κB, Tumor growth factor-beta (TGF-β), ubiquitination, viral inhibition of apoptosis, and resistance to ASFV infection. Prospects for developing a domestic pig that is resistant to ASFV are also discussed.

Overexpression of Pericentromeric HSAT2 DNA Increases Expression of EMT Markers in Human Epithelial Cancer Cell Lines.

Pericentromeric tandemly repeated DNA of human satellites 1, 2, and 3 (HS1, HS2, and HS3) is actively transcribed in some cells. However, the functionality of the transcription remains obscure. Studies in this area have been hampered by the absence of a gapless genome assembly. The aim of our study was to map a transcript that we have previously described as HS2/HS3 on chromosomes using a newly published gapless genome assembly T2T-CHM13, and create a plasmid overexpressing the transcript to assess the influence of HS2/HS3 transcription on cancer cells. We report here that the sequence of the transcript is tandemly repeated on nine chromosomes (1, 2, 7, 9, 10, 16, 17, 22, and Y). A detailed analysis of its genomic localization and annotation in the T2T-CHM13 assembly revealed that the sequence belonged to HSAT2 (HS2) but not to the HS3 family of tandemly repeated DNA. The transcript was found on both strands of HSAT2 arrays. The overexpression of the HSAT2 transcript increased the transcription of the genes encoding the proteins involved in the epithelial-to-mesenchymal transition, EMT (SNAI1, ZEB1, and SNAI2), and the genes that mark cancer-associated fibroblasts (VIM, COL1A1, COL11A1, and ACTA2) in cancer cell lines A549 and HeLa. Co-transfection of the overexpression plasmid and antisense nucleotides eliminated the transcription of EMT genes observed after HSAT2 overexpression. Antisense oligonucleotides also decreased transcription of the EMT genes induced by tumor growth factor beta 1 (TGFβ1). Thus, our study suggests HSAT2 lncRNA transcribed from the pericentromeric tandemly repeated DNA is involved in EMT regulation in cancer cells.

The role of bee venom on immunological and hematological parameters in albino rats

Bee venom (BV) showed therapeutical effects to treat various diseases as it contains at least 18 pharmacologically active components including various enzymes, peptides, and amines. This study aimed to evaluate the action of BV on some hematological parameters, humoral and cellular immunity, and the determination of antioxidant levels in male albino rats. The study included 40 male albino rats (190-210 g), divided into four groups. Three groups were injected subcutaneously with three different doses of BV (2.5, 5, and 10 mg/kg, respectively). The control group was injected with saline solution. Blood samples were obtained to measure total leucocytes count (TLC), differential leukocytes count, hematological parameters (hemoglobin (Hb), hematocrit (HCT), red blood cells (RBCs), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC) and Platelets. Sera were used to assess immunoglobulins (IgM, IgG, IgA, and IgE), some cytokines e.g., tumor necrosis factor-alpha (TNF-α), tumor growth factor beta (TGF-β), interleukins 6 and 10 (IL-6, IL-10), and some antioxidant levels malondialdehyde (MDA), super oxide dismutase (SOD), and glutathione (GSH). Data showed that BV therapy increased antibody production levels (IgM, IgG, and IgA) while decreasing IgE levels. Hematological markers (Hb and lymphocytes) were increased. BV increased total TGF- β and IL-10 but decreased total TNF- α and IL-6. On the antioxidant scale, an increase in SOD, CAT, and GSH levels was observed, accompanied by a decrease in MDA levels. However, the BV treatment led to a significant reduction in the number of eosinophils, monocytes, and neutrophils (p < 0.05). In conclusion, our findings suggested that BV may be utilized to increase the effectiveness of various immunological and hematological parameters.

Molecular and morphological alterations in uninjured skin of streptozotocin‐induced diabetic mice

Diabetes affects every tissue in the body, including the skin. The main skin problem is the increased risk of infections, which can lead to foot ulcers. Most studies evaluating the effects of diabetes on the skin are carried out in wound healing areas. There are fewer studies on uninjured skin, and some particularities of this tissue are yet to be elucidated. In general, cellular and molecular outcomes of diabetes are increased oxidative stress and lipid peroxidation. For our study, we used C57BL/6 mice that were divided into diabetic and non-diabetic groups. The diabetic group received low doses of streptozotocin on 5 consecutive days. To evaluate the effects of hyperglycemia on uninjured skin, we performed morphological analysis using hematoxylin/eosin staining, cellular analysis using Picrosirius red and Nissl staining, and immunostaining, and evaluated protein expression by polymerase chain reaction. We confirmed that mice were hyperglycemic, presenting all features related to this metabolic condition. Hyperglycemia caused a decrease in interleukin 6 (Il-6) and an increase in tumor necrosis factor alpha (Tnf-α), Il-10, F4/80, tumor growth factor beta (Tgf-β), and insulin-like growth factor 1 (Igf-1). In addition, hyperglycemia led to a lower cellular density in the epidermis and dermis, a delay in the maturation of collagen fibers, and a decrease in the number of neurons. Furthermore, we showed a decrease in Bdnf expression and no changes in Ntrk2 expression in the skin of diabetic animals. In conclusion, chronic hyperglycemia in mice induced by streptozotocin caused disruption of homeostasis even before loss of skin continuity.

Plumbagin attenuates Bleomycin-induced lung fibrosis in mice

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with limited treatment options. Plumbagin (PL) is an herbal extract with diverse pharmacological effects that have been recently used to treat various types of cancer. This study aims to explore the anti-fibrotic effect of PL and possible underlying mechanisms in IPF.MethodsWe used a bleomycin-induced experimental mouse model of lung fibrosis to assess the potential anti-fibrotic effect of PL. Histological analysis of lung tissue samples by H&E and Masson’s trichrome staining and hydroxyproline assay was performed to evaluate the fibrotic alterations. ELISA and real-time quantitative PCR were conducted to determine the amount of tumor necrosis factor-alpha (TNFα), tumor growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and endothelin-1 (ET-1).ResultsBleomycin exposure induced lung fibrosis, which was indicated by inflammation, collagen deposition, and structural damage. PL remarkably prevented bleomycin-induced lung fibrosis. Furthermore, PL significantly inhibited TNF-α and TGF-β production. PL also diminished the upregulated expression of CTGF and ET-1 induced by bleomycin.ConclusionOverall, our findings suggest PL as an anti-fibrotic agent acting via down-regulation of TGF-β/CTGF or ET-1 axis, as well as TNF-α, to improve lung fibrosis.

Tamarix articulata Induced Prevention of Hepatotoxicity Effects of In Vivo Carbon Tetrachloride by Modulating Pro-Inflammatory Serum and Antioxidant Enzymes to Reverse the Liver Fibrosis.

This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels.

Skin Anti-Aging Potential of Ipomoea pes-caprae Ethanolic Extracts on Promoting Cell Proliferation and Collagen Production in Human Fibroblasts (CCD-986sk Cells).

Collagen loss in the skin dermis is a major cause of age-related changes to the skin. Natural phytochemical substances are desirable for the prevention of skin aging and the formation of wrinkles. Ipomoea pes-caprae (IPC) has been utilized for nutritional and therapeutic purposes, and its extract contains collagenase inhibitory activity while causing no cytotoxicity. The purpose of this study was to examine the impact of IPC extracts on cell proliferation and collagen production in human fibroblasts (CCD-986sk cells). IPC leaves were macerated in 70% and 95% ethanol and the chemical composition of the resulting extracts (IPC70 and IPC95) were determined using high performance liquid chromatography (HPLC). The bioactivity of IPC extracts was examined in CCD-986sk cells, including antioxidant capacity, inhibition of collagenase, effects on cell proliferation and collagen production, as well as wound healing using an in vitro scratch test. Changes in expression of collagen type I (COL1A1), tumor growth factor beta 1 (TGFB1), and beta-fibroblast growth factor (FGF2) genes were also evaluated. The antioxidant and collagenase inhibitory properties of IPC extracts were associated with 3,5-di-caffeoylquinic acid, chlorogenic acid, and ferulic acid. IPC extracts at noncytotoxic concentrations significantly increased cell proliferation, collagen production, and wound healing. These effects appear linked to the upregulation of COL1A1, TGFB1, and FGF2 genes. The bioactivity of the IPC70 extract was greater than that for IPC95. This is useful in cosmeceutical applications for human skin aging. Our findings indicate that IPC extracts have the potential for use in skin anti-aging cosmeceutical preparations.

Oxidative Stress Enhances the TGF-β2-RhoA-MRTF-A/B Axis in Cells Entering Endothelial-Mesenchymal Transition.

Around 45% of deaths in the EU and the US are due to fibrotic diseases. Although myofibroblasts are detected in various fibrotic tissues, they are mostly transdifferentiated from endothelial cells during the endothelial-mesenchymal transition (EndMT) induced by tumor growth factor-beta (TGF-β) family members. Growing evidence indicates that oxidative stress might enhance the sensitivity and the effects of TGF-β stimulation; however, the molecular mechanisms involved in the coordination of oxidative stress and TGF-β inductions remain poorly understood. Our findings indicate for the first time that oxidative stress enhances mesenchymal trans-differentiation of human microvascular endothelial cells (HMEC-1 cells) and that the oxidative stress-dependent TGF-β2-RhoA/Rac1-MRTF-A axis is critical for the induction of later stages of EndMT. This additive effect was manifested in TGF-β1-stimulated and Snail-overexpressed cells, where it caused higher cell elongation and faster migration on collagen I layers. Additionally, Western blot assay indicated the presence of alterations in cell contraction and EndMT markers. We conclude that complex anti-fibrotic therapies based on the inhibition of MRTF activities and oxidative stress might be an attractive target for fibrosis treatment.

Exosomes derived from γδ-T cells synergize with radiotherapy and preserve antitumor activities against nasopharyngeal carcinoma in immunosuppressive microenvironment

BackgroundRadiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), but its therapeutic efficacy is poor in some patients due to radioresistance. Adoptive T cell-based immunotherapy has also shown promise...

High-resolution melting PCR analysis for genotyping the gene polymorphism of TNF-α, TGF-β1, IL-10, and IFN-γ in lung transplant recipients

High-resolution melting (HRM) analysis is a genotyping method which has the advantages of simple, rapid, low-cost and closed-tube operation.This study evaluated HRM analysis as an option for detecting the single nucleotide polymorphism (SNP) of cytokine, and profiled the distribution of cytokine gene polymorphism in the lung transplant recipients (LTRs).High-resolution melting-polymerase chain reaction (HRM-PCR) assays for genotyping tumor necrosis factor alpha (TNF-α) (-308 A/G), tumor growth factor beta 1 (TGF-β1) (+869 T/C), interleukin 10 (IL-10) (-592 C/A, -819 T/C, -1082 G/A), and interferon gamma (IFN-γ) (+874 T/A) SNPs were developed on the LightCycler® 480. The SNPs of the aforementioned cytokine genes in 322 LTRs and 266 normal controls were detected using HRM-PCR approach. To confirm the accuracy of the HRM-PCR assay, we randomly selected 100 samples from the LTRs and detected the aforementioned SNPs with sequence-specific primer-polymerase chain reaction (SSP-PCR) method, using a commercial kit.The data show that the HRM-PCR assay can distinguish all the cytokine SNPs, and the results of HRM-PCR analysis are in complete concordance to the genotyping results obtained using a commercial kit (κ = 1.0). Our data also show that the allele and genotype frequencies of the abovementioned cytokine are not significantly different between the LTRs and the control groups (p > 0.05). In addition, we found the genotypes of TGF-β1 +869 associated with high expression phenotype were prevalent in the LTRs. On the contrary, for TNF-α -308, IL-10 and IFN-γ, the genotypes associated with low expression phenotype were most common in the LTRs.In this study, we described a rapid, low-cost and high-throughput HRM-PCR technology for genotyping cytokine SNPs. Our data may be utilized for future studies examining the associations of cytokine gene polymorphisms with the prognosis of the LTRs.

Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Effects of electroacupuncture on the functionality of NG2-expressing cells in perilesional brain tissue of mice following ischemic stroke.

Neural/glial antigen 2 (NG2)-expressing cells has multipotent stem cell activity under cerebral ischemia. Our study examined the effects of electroacupuncture (EA) therapy (2 Hz, 1 or 3 mA, 20 minutes) at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic stroke. EA stimulation alleviated motor deficits caused by ischemic stroke, and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone, a free radical scavenger. The properties of NG2-expressing cells were altered with 1 mA EA stimulation, enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha expression. EA stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor, tumor growth factor beta, and neurotrophin 3. In the perilesional striatum, EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte, endothelial cell, and microglia/macrophage markers (CC1, CD31, and CD68). EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta signaling. Our results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor -induced signaling, subsequently ameliorating motor dysfunction. The animal experiments were approved by the Animal Ethics Committee of Pusan National University (approval Nos. PNU2019-2199 and PNU2019-2884) on April 8, 2019 and June 19, 2019.