Expression Of Factor Research Articles

Hydroxycitric Acid Tripotassium Hydrate Attenuates Monocrotaline and Hypoxia-Induced Pulmonary Hypertension in Rats.

Pulmonary hypertension was induced in male Sprague-Dawley rats by a single subcutaneous injection of monocrotaline or hypoxic chamber. In vivo, inflammatory cytokine (including TNF-α, IL-1β, IL-6, and TGF-β, the level of SOD) expression, superoxide dismutase and hydrogen peroxide levels, and p-IκBα and p65 expressions were detected. In vitro, pulmonary artery smooth muscle cell proliferation and migration, ROS production, and hypoxia-inducible factor-1 expression were also studied. Hydroxycitric acid tripotassium hydrate decreased right ventricular systolic pressure and reduced right ventricular fibrosis and pulmonary vascular remodeling in rats with two kinds of pulmonary hypertension. Moreover, the expression of both inflammatory and oxidative stress factors was effectively reduced, and the p65 signaling pathway was found to be inhibited in this study. Additionally, hydroxycitric acid tripotassium hydrate inhibited human pulmonary artery smooth cell proliferation and migration in vitro. This study shows that hydroxycitric acid tripotassium hydrate can alleviate pulmonary hypertension caused by hypoxia and monocycloline in rats, improve remodeling of the right ventricle and pulmonary artery, and inhibit pulmonary artery smooth muscle cell proliferation and migration. The protective effects may be achieved by regulating inflammation and oxidative stress through the p65 signaling pathway.

Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia.

Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate the immune resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity and suppresses the body's antitumor immune response. Herein, we have successfully immobilized and functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) to deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing the conversion of H2O2 to O2, thereby sensitizing cuproptosis. Meanwhile, increased tumor oxygenation suppresses the expression of the hypoxia-inducible factor-1 (HIF-1) protein, resulting in the alleviation of the immunosuppressive tumor microenvironment. Of note, cuproptosis induces immunogenic cell death (ICD), which facilitates dendritic cell (DC) maturation and enhances antigen presentation through polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation in tumor cells complements checkpoint blockers (αPD-L1), enhancing antitumor immunity. The strategy of enhancing cuproptosis-mediated antitumor immune responses by alleviating hypoxia effectively promotes the activation and proliferation of effector T cells, ultimately leading to long-term immunity against cancer.

Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts.

Cells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These "taste-like" cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. Public RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Gα-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligature-induced periodontitis mouse model using Ga-gustducin-null (Gnat3-/-) mice. The expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3-/- mice. Gingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via "SCC-like" activity. Salicin can activate Tas2r143-mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the "SCC-like" function of gingival fibroblasts.

Beckwith–Wiedemann syndrome with juvenile fibrous nodules and lobular breast tumors: a case report and review of the literature

BackgroundBeckwith–Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors. Notably however, reports of patients with BWS and breast tumors are rare, and the association between these conditions is still unclear. Insulin-like growth factor-2 (IGF2) expression is known to be associated with the development of various cancers, including breast cancer, and patients with BWS with specific subtypes of molecular defects are known to show characteristic clinical features and IGF2 overexpression.Case presentationA 17-year-old girl who had been diagnosed with BWS based on an umbilical hernia, hyperinsulinemia, and left hemihypertrophy at birth, visited our department with a gradually swelling left breast. Her left breast was markedly larger than her right breast on visual examination. Imaging examinations showed two tumors measuring about 10 cm each in the left breast, and she was diagnosed with juvenile fibroadenoma following core needle biopsy. The two breast tumors were removed surgically and the patient remained alive with no recurrence. The final diagnosis was juvenile fibroadenoma without malignant findings. Immunohistochemical staining using IGF2 antibody revealed overexpression of IGF2 in the cytoplasm of ductal epithelial cells. Because of her clinical features and IGF2 overexpression, molecular defects of 11p15.5 including a possible genetic background of paternal uniparental disomy of chromosome 11 or hypermethylation of imprinting center 1 was suspected.ConclusionsIn this case, overexpression of IGF2 suggested a possible relationship between BWS and breast tumors. Moreover, the characteristic clinical features and IGF2 staining predicted the subtype of 11p15.5 molecular defects in this patient.

An insight into the diagnostic, prognostic, and taxanes resistance of double zinc finger and homeodomain factor's expression in naïve prostate cancer.

The online version contains supplementary material available at 10.1007/s13205-024-03941-8.

Dietary feed nanozeolite, Pediococcus, and medium-chain fatty acid enhanced growth performance and transcription of growth-related gene of Nile tilapia (Oreochromis niloticus)

The current trial was designed to evaluate the positive impacts of different feed additives singly or in combination on the growth performance, nutritional parameters, intestinal histology, and gene expression of some growth and fat metabolism-related genes in the liver tissue of Nile tilapia. The experimented fish were allocated into eight groups in a glass aquarium (10 fish/aquarium in triplicate) with Pediococcus acidilactici, nanozeolites, and/or medium-chain fatty acid additives. The studied treatments were control (T0), nanozeolite (T1), Pediococcus (T2), medium-chain fatty acid (T3), nanozeolite + Pediococcus (T4), nanozeolite + medium-chain fatty acid (T5), Pediococcus + medium-chain fatty acid (T6), and nanozeolite + Pediococcus + medium-chain fatty acid (T7). The results of the growth and nutritional parameters (i.e., final body weight, total weight gain, feed intake, specific growth rate, feed conversion ratio, and protein efficiency ratio) of tilapia-fed diets supplemented with Pediococcus, nanozeolites, and medium-chain fatty acids improved, but the combination of these additives was significantly more effective. Moreover, expression of growth hormone receptor 1 gene was upregulated (P ≤ 0.05) in T7 fish when compared with T0, other groups showing intermediate values. Expression of insulin-like growth factor-1 was upregulated (P ≤ 0.05) in T5, T6, and T7 fish when compared with the other groups. The expression of the fatty acid-binding protein was higher in T6 and T7 fish (P ≤ 0.05) when compared with T0, T1, and T3 fish. In conclusion, combined additives had significant effects on improving growth and regulating growth-related genes.

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = -0.49), systolic blood pressure (SBP) (-0.44), and carotid intima-media thickness (cIMT) (-0.43). The IGF-1R expression was negatively correlated with PWV (r = -0.42) and SBP (r = -0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

Urtica pilulifera leaves extract mitigates cadmium induced hepatotoxicity via modulation of antioxidants, inflammatory markers and Nrf-2 signaling in mice.

Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of Urtica pilulifera leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl2) in mice. Methods: In vitro phytochemical screening and the metal-chelating activity of UPLE were ascertained. Four groups of forty male mice were used (n = 10) as follows; Group 1 (G1) was a negative control. G2 was injected i.p., with UPLE (100mg/kg b. wt) daily. G3 was injected i.p., with Cd (5mg/kg b. wt) daily. G4 was injected with Cd as in G3 and with UPLE as in G2. On day 11, the body weight changes were evaluated, blood, and serum samples were collected for hematological and biochemical assessments. Liver tissues were used for biochemical, molecular, and histopathological investigations. Results: The results showed that UPLE contains promising secondary metabolites that considerably lessen the negative effects of Cd on liver. Furthermore, UPLE inhibited oxidative stress and inflammation; restored antioxidant molecules; and promoted nuclear-related factor-2 (Nrf-2) expression. Also, UPLE improved the histopathological alterations induced by Cd. Discussion: This study explored the beneficial role of UPLE treatment in Cd-induced liver injury through enhancing Nrf-2 signaling and antioxidant enzyme gene expression in the liver of mice. Therefore, UPLE could have valuable implications against hepatotoxicity induced by environmental cadmium exposure. Which can be used as a chelating agent against Cd.

Modulating Th1/Th2 drift in asthma-related immune inflammation by enhancing bone mesenchymal stem cell homing through targeted inhibition of the Notch1/Jagged1 signaling pathway

Asthma, a disease intricately linked to immune inflammation, is significantly influenced by the immune regulatory effect of bone mesenchymal stem cells (BMSCs). This study aims to investigate changes in the homing of BMSCs in bronchial asthma, focusing on the Notch homolog (Notch)1/Jagged1 signaling pathway’s role in regulating T helper 1(Th1)/T helper 2(Th2) drift. Additionally, we further explore the effects and mechanisms of homologous BMSCs implantation in asthma-related immune inflammation. Following intervention with BMSCs, a significant improvement in the pathology of rats with asthma was observed. Simultaneously, a reduction in the expression of inflammatory cells and inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin(IL)-4, and IL-13 was observed in bronchoalveolar lavage fluid (BALF). Furthermore, there was an increase in the expression of Th1 cytokine Interferon-γ（IFN-γ）and the transcription factor T-box expressed in T cell (T-bet), while the expression of Th2 cytokine IL-13 and transcription factor GATA binding protein (GATA)-3 decreased in lung tissue. This indicates that the Th1/Th2 drift leans towards Th1, which a crucial in ameliorating asthma inflammation. Importantly, inhibition of the Notch1 signaling pathway led to an increased expression of the Stromal cell-derived factor-1(SDF-1)/C-X-C motif chemokine receptor (CXCR)4 chemokine axis. Consequently, the homing ability of bone marrow mesenchymal stem cells to asthma-affected lung tissue was significantly enhanced. BMSCs demonstrated heightened efficacy in regulating the cytokine/chemokine network and Th1/Th2 balance, thereby restoring a stable state during the immune response process in asthma. In conclusion, inhibiting the Notch signaling pathway enhances the expression of the SDF-1 and CXCR4 chemokine axis, facilitating the migration of allogeneic BMSCs to injured lung tissues. This, in turn, promotes immune regulation and improves the Th1/Th2 imbalance, thereby enhancing the therapeutic effect on asthmatic airway inflammation.

Impact of Growth Hormone on Microglial and Astrocytic Function.

The role of growth hormone (GH) in the central nervous system (CNS) involves neuroprotection, neuroregeneration, formation of axonal projections, control of cognition, and regulation of metabolism. As GH induces insulin-like growth factor-1 (IGF-1) expression in many tissues, differentiating the specific functions of GH and IGF-1 in the organism is a significant challenge. The actions of GH and IGF-1 in neurons have been more extensively studied than their functions in nonneuronal cells (e.g., microglial cells). Glial cells are fundamentally important to CNS function. Microglia, astrocytes, oligodendrocytes, and tanycytes are essential to the survival, differentiation, and proliferation of neurons. As the interaction of the GH/IGF-1 axis with glial cells merits further exploration, our objective for this review was to summarize and discuss the available literature regarding the genuine effects of GH on glial cells, seeking to differentiate them from the role played by IGF-1 action whenever possible.

Novel insights into heat tolerance: the impact of dwarf and frizzled feather traits on crossbreed chicken performance under thermal stress

Heat stress (HS) poses significant challenges to broiler production, negatively influencing growth performance and meat quality. This study explores the resilience and the meat quality of hybrid chickens with dwarf size and frizzled feather traits to HS. We investigated F1 progeny derived from a crossbreed of dwarf yellow chickens (DYCs) with Yuexi frizzled feather chickens. Following a rearing period of 12 weeks, we randomly assigned 72 chickens into two distinct environmental conditions: a HS group subjected to 35 ± 1 °C for 8 h per day, and a control group (CN) maintained at 26 ± 1 °C. Seven days post-HS, multiple tissue samples were collected to assess meat quality attributes and measure expression levels of heat shock proteins (HSPs), muscle growth-related genes and cytokines. The results demonstrated a substantial reduction in weight gain of the F1 chickens exposed to HS, along with decreased expression of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the liver. Furthermore, HS exposure significantly increased muscle shear force and the expression of HSP70 in both liver and pectoral muscle tissues (p < .05). Despite these changes, there were no significant alterations in the other meat quality indices, or indicators of splenic and hepatic tissue injury. Likewise, expression levels of growth hormone receptor (GHR) and cytokines remained stable, implying a lack of heightened inflammation. These observations suggest an inherent thermotolerance in the chickens possessing dwarf size and frizzled feather traits, warranting further exploration for their potential in heat-stress-prone poultry production environments. Highlights Dwarf and frizzled feather traits in crossbreed chickens show potential for improved heat tolerance in poultry production. Heat stress had limited impact on meat quality parameters, suggesting resilience of these local chicken traits. Understanding the genetic basis of thermotolerance can inform breeding strategies for climate-resilient chickens.

Supplementing the Diet of Hybrid Grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) with Compound Acidifier Is a Good Way to Alleviate Poor Intestinal Growth Caused by High Levels of Cottonseed Protein Concentrate

This study investigated the effect of adding the compound acidifiers on the intestine health of hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) fed diet with higher cottonseed protein concentrate (CPC). To assess the benefits of compound acidifiers helping CPC to replace more fish meal (FM) for hybrid grouper, five isonitrogen and isolipid experimental diets were formulated. The five diets consisted of a control diet (FM, 50%) and four experimental diets (27.5% FM, 27.27% CPC), each of which contained compound acidifiers to varying degrees (FCA0, FCA0.05, FCA0.1, and FCA0.2). Each diet was fed to three replicates of each group for 8 weeks. In the FCA0.05 group, the results demonstrated a statistically significant increase in protein efficiency ratio, lipid efficiency ratio, and the activity of digestive enzymes in the intestine (P &lt; 0.05). In the FCA0.05 group, there was a clearly enhanced expression of anti‐inflammatory cytokines in the intestines (P &lt; 0.05). In the FCA0.1 group, there may be an increase in the expression of important genes involved in fatty acid metabolism in the intestinal (P &lt; 0.05). Appropriate compound acidifiers decreased the relative abundance of Vibrio and other harmful bacteria in the intestine flora that were brought by high CPC. In conclusion, when the hybrid grouper was given a diet containing more CPC, the FCA0.05 group was able to promote intestinal development, enhance digestive enzyme activity and feed consumption, raise antioxidant enzyme activity and anti‐inflammatory factor expression, and improve intestinal health.

Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.

Rationale: The surge of severe liver damage underscores the necessity for identifying new targets and therapeutic agents. Endoplasmic reticulum (ER) stress induces ferroptosis with Gα12 overexpression. NF-κB essential modulator (NEMO) is a regulator of inflammation and necroptosis. Nonetheless, the regulatory basis of NEMO de novo synthesis and its impact on hepatocyte ferroptosis need to be established. This study investigated whether Nrf2 transcriptionally induces IKBKG (the NEMO gene) for ferroptosis inhibition and, if so, how NEMO induction protects hepatocytes against ER stress-induced ferroptosis. Methods: Experiments were conducted using human liver tissues, hepatocytes, and injury models, incorporating NEMO overexpression and Gα12 gene modulations. RNA sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation analyses were done. Results: NEMO downregulation connects closely to ER and oxidative stress, worsening liver damage via hepatocyte ferroptosis. NEMO overexpression protects hepatocytes from ferroptosis by promoting glutathione peroxidase 4 (GPX4) expression. This protective role extends to oxidative and ER stress. Similar shifts occur in nuclear factor erythroid-2-related factor-2 (Nrf2) expression alongside NEMO changes. Nrf2 is newly identified as an IKBKG (NEMO gene) transactivator. Gα12 changes, apart from Nrf2, impact NEMO expression, pointing to post-transcriptional control. Gα12 reduction lowers miR-125a, an inhibitor of NEMO, while overexpression has the opposite effect. NEMO also counters ER stress, which triggers Gα12 overexpression. Gα12's significance in NEMO-dependent hepatocyte survival is confirmed via ROCK1 inhibition, a Gα12 downstream kinase, and miR-125a. The verified alterations or associations within the targeted entities are validated in human liver specimens and datasets originating from livers subjected to exposure to other injurious agents. Conclusions: Hepatic injury prompted by ER stress leads to the suppression of NEMO, thereby facilitating ferroptosis through the inhibition of GPX4. IKBKG is transactivated by Nrf2 against Gα12 overexpression responsible for the increase of miR-125a, an unprecedented NEMO inhibitor, resulting in GPX4 induction. Accordingly, the induction of NEMO mitigates ferroptotic liver injury.

Insulin-like growth factor-1 expression levels in pro-inflammatory response in calves with neonatal systemic inflammatory response syndrome

The objective of this study was to investigate the mRNA expression of insulin-like growth factor-1 (IGF-1), pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α), serum immunoglobulin profiles (IgG and IgM), and lipid peroxidation status (MDA) in relation to pro-inflammatory cytokines. A case-controlled, prospective, and observational investigation was completed on 85 calves. Total RNA was isolated from whole blood samples of both the SIRS and healthy calves, followed by reverse transcription into cDNA. The resulting cDNAs were mixed with iTaq Universal SYBR Green Supermix and primers specific to the relevant genes using the Rotor-Gene Q instrument. After the reaction was completed, gene expressions were normalised against β-actin using the 2-ΔΔCT method. The mRNA levels of pro-inflammatory cytokines namely (IL-1β [SIRS: 2.15 ± 0.55, Control: 1.13 ± 0.62; P = 0.001], IL-6 [SIRS: 2.82 ± 0.52, Control: 0.91 ± 0.11; P < 0.001], IL-18 [SIRS: 1.92 ± 0.41, Control: 0.99 ± 0.13; P < 0.001], and TNF-α [SIRS: 2.59 ± 0.28, Control: 0.93 ± 0.09; P < 0.001]) and IGF-1 (SIRS: 3.55 ± 0.55, Control: 0.91 ± 0.15; P < 0.001) were up-regulated in calves with SIRS, while serum IgG (SIRS: 4.16 ± 0.26, Control: 1.73 ± 0.17; P < 0.001), IgM (SIRS: 1.55 ± 0.11, Control: 1.09 ± 0.13; P < 0.001), and MDA levels (SIRS: 41.12 ± 3.48, Control: 3.76 ± 0.81; P < 0.001) increased significantly in these calves. Furthermore, significant (P < 0.01) positive correlations were found in calves with SIRS in relation to the expression levels of IL-1β, IL-6, IL-18, TNF-α, IGF-1, serum immunoglobulins, and MDA levels. These results suggest that IGF-1 could be a valuable pro-inflammatory marker, considering its high positive correlation with the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and markers (MDA, IgG, and IgM) in calves with SIRS.

Canine follicular cell and medullary thyroid carcinomas: Immunohistochemical characterization

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs ( P= .041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs ( P = .001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs ( P = .011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation.

Prepared MW-Immunosensitizers Precisely Release NO to Downregulate HIF-1α Expression and Enhance Immunogenic Cell Death.

Microwave thermotherapy (MWTT) has limited its application in the clinic due to its high rate of metastasis and recurrence after treatment. Nitric oxide (NO) is a gaseous molecule that can address the high metastasis and recurrence rates after MWTT by increasing thermal sensitivity, down-regulating the expression of hypoxia-inducible factor-1 (HIF-1), and inducing the immunogenic cell death (ICD). Therefore, GaMOF-Arg is designed, a gallium-based organic skeleton material derivative loaded with L-arginine (L-Arg), and coupled the mitochondria-targeting drug of triphenylphosphine (TPP) on its surface to obtain GaMOF-Arg-TPP (GAT) MW-immunosensitizers. When GAT MW-immunosensitizers are introduced into mice through the tail vein, reactive oxygen species (ROS) are generated and L-Arg is released under MW action. Then, L-Arg reacts with ROS to generate NO, which not only downregulates HIF-1 expression to improve tumor hypoxia exacerbated by MW, but also enhances immune responses by augment calreticulin (CRT) exposure, high mobility group box 1 (HMGB1) release, and T-cell proliferation to achieve prevention of tumor metastasis and recurrence. In addition, NO can induce mitochondria damage to increase their sensitivity to MWTT. This study provides a unique insight into the use of metal-organic framework MW-immunosensitizers to enhance tumor therapy and offers a new way to treat cancer efficiently.

Ferulic acid attenuated diethylnitrosamine-provoked hepato-renal damage and malfunction by suppressing oxidative stress, abating inflammation and upregulating nuclear factor erythroid related factor-2 signaling

Background Diethylnitrosamine (DEN) is a potent environmental toxin that can reach humans through the food chain. It induces proliferative, degenerative and cancerous lesions in the liver and kidneys. Objective The principal goal of the existing research was to assess the preventive impacts of ferulic acid (FA) versus DEN- provoked hepato-renal damage and malfunction. Materials and methods Adult male rats were divided into four groups: group 1 (normal control) animals orally received saline every day for 14 weeks; group 2 (DEN) animals intraperitoneally received DEN (150 mg/kg twice a week) for 2 weeks; group 3 (DEN + FA) animals were injected intraperitoneally twice a week with DEN for 2 weeks besides to oral administration of FA (100 mg/kg/day) for 14 weeks; group 4 (FA) animals were given a similar dose of FA for a similar period. Results The results revealed that FA treatment reversed the DEN-mediated elevation in serum values of the liver enzymes activities as well as urea and creatinine levels; it also augmented the hepato-renal antioxidant system that overcame DEN-induced oxidative stress deteriorations. Moreover, FA markedly reduced the DEN-induced elevated hepato-renal levels of immuno-inflammatory markers (IL-1β and TNF-α) as well as downregulated the inflammatory mediators (Bcl-2, NF-κB, and nuclear factor erythroid related factor-2 (Nrf-2)), reflecting its protective potential. Conclusion The existing results elucidate that ferulic acid could prevent and ameliorate DEN-induced hepato-renal toxicological changes and can restore livers and kidneys’ functions; this effect could be mechanized through activation of anti-inflammatory and antioxidant systems, as well as regulation of NF-κB, Bcl2, and nuclear factor erythroid related factor-2 expression.

Lysine-rich rice partially enhanced the growth and development of skeletal system with better skeletal microarchitecture in young rats

Rice is the primary staple food for half of the world's population but is low in lysine content. Previously, we developed transgenic rice with enhanced free lysine content in rice seeds (lysine-rich rice), which was shown safe for consumption and improved the growth in rats. However, the effects of lysine-rich rice on skeletal growth and development remained unknown. In this study, we hypothesized that lysine-rich rice improved skeletal growth and development in weaning rats. Male weaning Sprague–Dawley rats received lysine-rich rice (HFL) diet, wild-type rice (WT) diet, or wild-type rice with various contents of lysine supplementation diet for 70 days. Bone microarchitectures were examined by microcomputed tomography, bone strength was investigated by mechanical test, and dynamics of bone growth were examined by histomorphometric analysis. In addition, we explored the molecular mechanism of lysine and skeletal growth through biochemical testing of growth hormone, bone turnover marker, and amino acid content of rat serum analysis, as well as in a cell culture system. Results indicated that the HFL diet improved rats' bone growth, strength, and microarchitecture compared with the WT diet group. In addition, the HFL diet increased the serum essential amino acids, growth hormone (insulin-like growth factor-1), and bone formation marker concentrations. The cell culture model showed that lysine deficiency reduced insulin-like growth factor-1 and Osterix expression, Akt/mammalian target of rapamycin signaling, and matrix mineralization, and inhibited osteoblast differentiation associated with bone growth. Our findings showed that lysine-rich rice improved skeletal growth and development in weaning rats. A further increase of rice lysine content is highly desirable to fully optimize bone growth and development.

Effects of the Supercritical Fluid Extract of Magnolia figo on Inducing the Apoptosis of Human Non-Small-Cell Lung Cancer Cells

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of M. figo (FMO) can induce apoptosis in A549, a human non-small-cell lung cancer cell line. The cell viability was assessed using an MTT assay. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and flow cytometry analysis were conducted. The expression of factors was assessed through Western blotting analyses. Gas chromatography–mass spectrometry (GC-MS) was performed. The results revealed that FMO treatment exhibited cytotoxicity, demonstrating dose-dependent effects. The TUNEL analysis and flow cytometry analysis revealed that FMO induced apoptosis in A549 cells. The Western blotting analysis revealed that FMO upregulated the expression of p53 and Bax protein, and downregulated the expression of Bcl-2 protein. The GC-MS analysis revealed eight components identified in FMO. These findings indicate that FMO can induce A549 apoptosis through the p53/Bcl-2/Bax pathways, confirming the apoptotic effects of M. figo on lung cancer cells. These results highlight the potential, for the first time, of M. figo as a source for developing novel drugs for lung cancer treatment.

Hydrolyzed Collagen Tripeptide Promotes Longitudinal Bone Growth in Childhood Rats via Increases in Insulin-Like Growth Factor-1 and Bone Morphogenetic Proteins.

Previous studies have reported that collagen tripeptide (CTP) derived from collagen hydrolysate has various beneficial effects on health by protecting against skin aging and improving bone formation and cartilage regeneration. Collagen-Tripep20TM (CTP20), which is a low-molecular-weight CTP derived from fish skin, contains a bioactive CTP, Gly-Pro-Hyp >3.2% with a tripeptide content >20%. Herein, we investigated the osteogenic effects and mechanisms of CTP20 (<500 Da) on MG-63 osteoblast-like cells and SW1353 chondrocytes. And we measured promoting ratio of the longitudinal bone growth in childhood rats. First, CTP20 at 100 μg/mL elevated the proliferation (15.0% and 28.2%), alkaline phosphatase activity (29.3% and 32.0%), collagen synthesis (1.25- and 1.14-fold), and calcium deposition (1.18- and 1.15-fold) in MG-63 cells and SW1353, respectively. In addition, we found that CTP20 could promote the longitudinal growth and height of the growth plate of the tibia in childhood rats. CTP20 enhanced the protein expression of insulin-like growth factor-1 (IGF-1) in MG-63 and SW1353 cells, and in the growth plate of childhood rats, along with Janus Kinase 2, and signal transducer and activator of transcription 5 activation in MG-63 and SW1353 cells. CTP20 also elevated the expression levels of bone morphogenetic proteins (BMPs) in MG-63 and SW1353 cells and in the growth plates of childhood rats. These results indicate that CTP20 may promote the endochondral ossification and longitudinal bone growth, through enhancing of IGF-1 and BMPs. (Clinical Trial Registration number: smecae 19-09-01).