An Aloe-Based Composition Constituting Polysaccharides and Polyphenols Protected Mice against D-Galactose-Induced Immunosenescence.

A decline in immune response, exhibited in the form of immunosenescence and inflammaging, is an age-associated disturbance of the immune system known to predispose the elderly to a greater susceptibility to infection and poor vaccine response. Polysaccharides and polyphenols from botanicals are known for their immune modulation effects. Here we evaluated a standardized mushroom-based composition, UP360, from Aloe barbadensis, Poria cocos, and Rosmarinus officinalis, as a natural nutritional supplement for a balanced immune response in an accelerated aging mouse model. Immunosenescence was induced by continual subcutaneous injection of D-galactose (D-gal) at a dose of 500 mg/kg/day to CD-1 mice. UP360 was administered at oral doses of 200 and 400 mg/kg to the mice starting on the 5th week of D-gal injection. The study lasted for a total of 9 weeks. All mice were given a quadrivalent influenza vaccine at 3 µg/animal via intramuscular injection 14 days before the end of the study. A group of D-gal-treated mice treated at 400 mg/kg/day UP360 was kept without vaccination. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis. UP360 was found to improve the immune response as evidenced by stimulation of innate and adaptive immune responses, increase antioxidant capacity as reflected by augmented SOD and Nrf2, and preserve vital immune organs, such as the thymus, from aging-associated damage. The findings depicted in this report show the effect of the composition in activating and maintaining homeostasis of the immune system both during active infections and as a preventive measure to help prime the immune system. These data warrant further clinical study to explore the potential application of the mushroom-based composition as an adjunct nutritional supplement for a balanced immune response.

Loss of mitogen-activated protein kinase phosphate-5 aggravates islet dysfunction in mice with type 1 and type 2 diabetes.

Impaired functionality and loss of islet ß-cells are the primary abnormalities underlying the pathogenesis of both type 1 and 2 diabetes (T1DM and T2DM). However, specific therapeutic and preventive mechanisms underlying these conditions remain unclear. Mitogen-activated protein kinase phosphatase-5 (MKP-5) has been implicated in carcinogenesis, lipid metabolism regulation, and immune cell activation. In a previous study, we demonstrated the involvement of exogenous MKP-5 in the regulation of obesity-induced T2DM. However, the role of endogenous MKP-5 in the T1DM and T2DM processes is unclear. Thus, mice with MKP-5 knockout (KO) were generated and used to establish mouse models of both T1DM and T2DM. Our results showed that MKP-5 KO exacerbated diabetes-related symptoms in mice with both T1DM and T2DM. Given that most phenotypic studies on islet dysfunction have focused on mice with T2DM rather than T1DM, we specifically aimed to investigate the role of endoplasmic reticulum stress (ERS) and autophagy in T2DM KO islets. To accomplish this, we performed RNA sequence analysis to gain comprehensive insight into the molecular mechanisms associated with ERS and autophagy in T2DM KO islets. The results showed that the islets from mice with MKP-5 KO triggered 5' adenosine monophosphate-activated protein kinase (AMPK)-mediated autophagy inhibition and glucose-regulated protein 78 (GRP-78)-dominated ERS. Hence, we concluded that the autophagy impairment, resulting in islet dysfunction in mice with MKP-5 KO, is mediated through GRP-78 involvement. These findings provide valuable insights into the molecular pathogenesis of diabetes and highlight the significant role of MKP-5. Moreover, this knowledge holds promise for novel therapeutic strategies targeting MKP-5 for diabetes management.

Discovery of Transfer Factors in Plant-Derived Proteins and an In Vitro Assessment of Their Immunological Activities.

Repeated exposure to pathogens leads to evolutionary selection of adaptive traits. Many species transfer immunological memory to their offspring to counteract future immune challenges. Transfer factors such as those found in the colostrum are among the many mechanisms where transfer of immunologic memory from one generation to the next can be achieved for an enhanced immune response. Here, a library of 100 plants with high protein contents was screened to find plant-based proteins that behave like a transfer factor moiety to boost human immunity. Aqueous extracts from candidate plants were tested in a human peripheral blood mononuclear cell (PBMC) cytotoxicity assay using human cancerous lymphoblast cells-with K562 cells as a target and natural killer cells as an effector. Plant extracts that caused PBMCs to exhibit enhanced killing beyond the capability of the colostrum-based transfer factor were considered hits. Primary screening yielded an 11% hit rate. The protein contents of these hits were tested via a Bradford assay and Coomassie-stained SDS-PAGE, where three extracts were confirmed to have high protein contents. Plants with high protein contents underwent C18 column fractionation using methanol gradients followed by membrane ultrafiltration to isolate protein fractions with molecular weights of <3 kDa, 3-30 kDa, and >30 kDa. It was found that the 3-30 kDa and >30 kDa fractions had high activity in the PBMC cytotoxicity assay. The 3-30 kDa ultrafiltrates from the top two hits, seeds from Raphanus sativus and Brassica juncea, were then selected for protein identification by mass spectrometry. The majority of the proteins in the fractions were found to be seed storage proteins, with a low abundance of proteins involved in plant defense and stress response. These findings suggest that Raphanus sativus or Brassica juncea extracts could be considered for further characterization and immune functional exploration with a possibility of supplemental use to bolster recipients' immune response.

A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction.

HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.

UP360, a Standardized Composition from Extracts of Aloe barbadense, Poria cocos, and Rosemary officinalis Protected Against Sepsis and Mitigated Acute Lung Injury in Murine Models.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated and unbalanced immune response to microbial infection. Restoring immune homeostasis and infection control are considered the primary strategies to manage sepsis. Natural bioactives such as polysaccharide and polyphenols from botanicals are known for their immune modulation activity. In this study, we evaluated a standardized aloe-based composition, UP360 (constitute of polysaccharides from Aloe barbadense and Poria cocos and polyphenols from Rosemary officinalis) in lipopolysaccharide (LPS)-induced sepsis and acute inflammatory lung injury murine models. Prophylactic oral administration of UP360 for 7 days at an oral dose of 500 mg/kg improved the survival rate of mice by 62.5%, whereas all mice in the vehicle control group were deceased 82 h after LPS injection. The merit of combining these traditional herbs to yield the standardized composition UP360 was also demonstrated in this model with a mortality rate of only 30.8%, whereas 76.9%, 53.9%, and 61.5% were recorded for each individual constituents A. barbadense, P. cocos, and R. officinalis, respectively. Dose-correlated statistically significant reductions in proinflammatory cytokines and chemokine tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-3 were observed for UP360 when administered at 250 and 500 mg/kg orally for 7 days before induction of acute lung injury (ALI) model in rats. The histopathology data from lung showed statistically significant 37.9% and 37% reductions in the overall lung damage severity and pulmonary edema, respectively, for UP360-treated rats. The aloe-based composition UP360 effectively improved the survival rate of septic animals and mitigated the severity of LPS-induced ALI in vivo. These data warrant further investigation of the composition for a potential application in human as an adjunct supplement in respiratory distress and sepsis.

One-Step Treatment for Upgrading Bleached Bamboo Pulp to Dissolving Pulp High Solvency in Green Alkali/Urea Aqueous Solution.

Bleached bamboo pulp, as a kind of natural cellulose, has received significant attention in the field of biomass materials due to its advantages of environmental protection and the abundance of raw materials. Low-temperature alkali/urea aqueous system is a green dissolution technology for cellulose, which has promising application prospects in the field of regenerated cellulose materials. However, bleached bamboo pulp, with high viscosity average molecular weight (Mη) and high crystallinity, is difficult to dissolve in an alkaline urea solvent system, restraining its practical application in the textile field. Herein, based on commercial bleached bamboo pulp with high Mη, a series of dissolvable bamboo pulps with suitable Mη was prepared using a method of adjusting the ratio of sodium hydroxide and hydrogen peroxide in the pulping process. Due to the hydroxyl radicals being able to react with hydroxyls of cellulose, molecular chains are cut down. Moreover, several regenerated cellulose hydrogels and films were fabricated in an ethanol coagulation bath or a citric acid coagulation bath, and the relationship between the properties of the regenerated materials and the Mη of the bamboo cellulose was systematically studied. The results showed that hydrogel/film had good mechanical properties, as the Mη is 8.3 × 104 and the tensile strength of a regenerated film and the film have values up to 101 MPa and 3.19 MPa, respectively. In this contribution, a simple method of a one-step oxidation of hydroxyl radicals to prepare bamboo cellulose with diversified Mη is presented, providing an avenue for a preparation of dissolving pulp with different Mη in an alkali/urea dissolution system and expanding the practical applications of bamboo pulp in biomass-based materials, textiles, and biomedical materials.

Fabrication of Superhydrophobic/Superoleophilic Bamboo Cellulose Foam for Oil/Water Separation.

Water is an indispensable strategic resource for biological and social development. The problem of oily wastewater pollution originating from oil spillages, industrial discharge and domestic oil pollution has become an extremely serious international challenge. At present, numerous superwetting materials have been applied to effectively separate oil and water. However, most of these materials are difficult to scale and their large-scale application is limited by cost and environmental protection. Herein, a simple, environmentally friendly strategy including sol-gel, freeze-drying and surface hydrophobic modification is presented to fabricate a bamboo cellulose foam with special wetting characteristics. The bamboo cellulose foam is superhydrophobic, with a water contact angle of 160°, and it has the superoleophilic property of instantaneous oil absorption. Owing to the synergistic effect of the three-dimensional network structure of the superhydrophobic bamboo cellulose foam and its hydrophobic composition, it has an excellent oil-absorption performance of 11.5 g/g~37.5 g/g for various types of oil, as well as good recyclability, with an oil (1,2-dichloroethane) absorption capacity of up to 31.5 g/g after 10 cycles. In addition, the prepared cellulose-based foam exhibits an outstanding performance in terms of acid and alkali corrosion resistance. Importantly, owing to bamboo cellulose being a biodegradable, low-cost, natural polymer material that can be easily modified, superhydrophobic/superoleophilic bamboo cellulose foam has great application potential in the field of oily wastewater treatment.

Dichotomous Roles of Men1 in Macrophages and Fibroblasts in Bleomycin-Induced Pulmonary Fibrosis.

Pulmonary fibrosis therapy is limited by the unclear mechanism of its pathogenesis. C57BL/6 mice were used to construct the pulmonary fibrosis model in this study. The results showed that Men1, which encodes menin protein, was significantly downregulated in bleomycin (BLM)-induced pulmonary fibrosis. Mice were made to overexpress or had Men1 knockdown with adeno-associated virus (AAV) infection and then induced with pulmonary fibrosis. BLM-induced pulmonary fibrosis was attenuated by Men1 overexpression and exacerbated by Men1 knockdown. Further analysis revealed the distinct roles of Men1 in fibroblasts and macrophages. Men1 inhibited fibroblast activation and extracellular matrix (ECM) protein expression while promoting macrophages to be profibrotic (M2) phenotype and enhancing their migration. Accordingly, pyroptosis was potentiated by Men1 in mouse peritoneal macrophages (PMCs) and lung tissues upon BLM stimulation. Furthermore, the expression of profibrotic factor OPN was positively regulated by menin in Raw264.7 cells and lung tissues by binding to the OPN promoter region. Taken together, although Men1 showed antifibrotic properties in BLM-induced pulmonary fibrosis mice, conflictive roles of Men1 were displayed in fibroblasts and macrophages. The profibrotic role of Men1 in macrophages may occur via the regulation of macrophage pyroptosis and OPN expression. This study extends the current pathogenic understanding of pulmonary fibrosis.

Noxa and Puma genes regulated by hTERT promoter can mitigate growth and induce apoptosis in hepatocellular carcinoma mouse model.

With significant high incidence and death rates, liver cancer has become one of the most common cancers all over the world. Hence, novel strategies are needed for the management of this malignancy. Apoptotic related proteins Noxa and Puma are the members of BH3-only family. In this study, human Noxa or Puma coding sequences have been inserted into plasmid pcDNA 3.1 regulated by human TERT promoter. The transfection of HepG2 cells with pcTERT-Noxa or pcTET-Puma resulted in the significant suppression of cell proliferation as well as finally led to apoptosis via mitochondrial and death receptor pathways, and also exhibited significantly reduced the ability of invasion and metastasis. Moreover, an in vivo study revealed that intratumoral injections of pcTERT-Noxa or pcTERT-Puma plasmids effectively suppressed the tumor growth and can exhibit anti-neoplastic effects by recruiting CD3, CD8, CD45 positive T lymphocytes in the tumor tissues. Overall, our findings illustrated that pcTERT-Noxa and pcTERT-Puma may exhibit significant anti-tumor effects both in vivo and in vivo.

Cell membrane breakage and triggering T cell infiltration are involved in human telomerase reverse transcriptase (hTERT) promoter-driven novel peptide KK-64 for liver cancer gene therapy.

Liver cancer is an aggressive malignancy with exhibits both high mortality and morbidity. The current treatment options are associated with several limitations, novel specific anti-cancer drugs are urgently needed to improve liver cancer treatment. In this study, a new peptide KK-64 was designed, and it showed strong cytotoxicity against liver cancer cells. To obtain the tumor targeting property, a plasmid that contains KK-64 DNA fragment and driven by human telomerase reverse transcriptase (hTERT) promoter was constructed. pcTERT-kk-64 plasmid was found to specifically inhibit the viability of liver cancer cells HepG2, induce substantial apoptosis as well as damage to the cell membranes, but had minimal effects toward normal liver HL-7702 cells. Furthermore, pcTERT-kk-64 plasmids was also noted to significantly attenuate migration and invasion of HepG2 cells. The anti-tumor effect of pcTERT-kk-64 plasmid was also observed in H22 cell-bearing mice, and it appeared to cause significant tumor regression, trigger tumor cell apoptosis, and infiltrate cytotoxicity T cells to the tumor tissues after plasmids injection. Thus, pcTERT-kk-64 plasmids showed both strong cytotoxicity and tumor selectivity in vitro and in tumor-bearing mice in liver cancer models.

Cephalometric craniofacial features of patients with Sagliker syndrome: a primary analysis of our experience.

BACKGROUND: Sagliker syndrome (SS) is characterized by a severe uglifying facial appearance resulting from untreated or inadequately treated secondary hyperparathyroidism (SHPT). To date, the craniofacial morphology of patients with SS has yet to be analyzed. The present research sought to cephalometrically evaluate the craniofacial features of patients with SS and to perform an in-depth analysis of their serum biochemical parameters, with the aim of furthering the theoretical basis for the early diagnosis and prevention of SS. METHODS: A retrospective chart review of 9 patients who fulfilled the diagnostic criteria for SS were included in this study, and their serum biochemical parameters were collected. After subjecting standard lateral cephalometric radiographic images to correction for distortions caused by magnification followed by digitization, we conducted a cephalometric analysis. Student's two-tailed t tests or Mann-Whitney U tests were used to analyze the data. Thirty-three patients with patients with SHPT alone were also included as controls. RESULTS: The lower anterior facial height (ANS-ME) and total anterior facial height (N-Me) measurements of patients with SS were significantly increased compared to those of the controls. The angles between the Frankfort horizontal, palatal, and occlusal planes and the mandibular plane, were greater in the SS group than in the control group, as was the gonial angle. Patients with SS also exhibited a significantly larger maxillary protrusion angle and relative position of the maxilla to the mandible. Most patients with SS had class II malocclusion, whereas most of the controls exhibited normal occlusion. Soft tissue largely followed the same pattern as craniofacial changes. Our investigation also showed that among patients with SHPT, female sex, longer duration of dialysis, and higher serum levels of alkaline phosphatase and intact parathyroid hormone were associated with development to SS. CONCLUSIONS: Patients with SS show facial and biochemical differences compared to patients with SHPT. Female sex, long dialysis duration, and high serum levels of intact parathyroid hormone and alkaline phosphatase may be potential risk factors for SS.

Analysis of immune cell components and immune-related gene expression profiles in peripheral blood of patients with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by severe loss of pancreatic ß cells. Immune cells are key mediators of ß cell destruction. This study attempted to investigate the role of immune cells and immune-related genes in the occurrence and development of T1DM. METHODS: The raw gene expression profile of the samples from 12 T1DM patients and 10 normal controls was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by Limma package in R. The least absolute shrinkage and selection operator (LASSO)-support vector machines (SVM) were used to screen the hub genes. CIBERSORT algorithm was used to identify the different immune cells in distribution between T1DM and normal samples. Correlation of the hub genes and immune cells was analyzed by Spearman, and gene-GO-BP and gene-pathway interaction networks were constructed by Cytoscape plug-in ClueGO. Receiver operating characteristic (ROC) curves were used to assess diagnostic value of genes in T1DM. RESULTS: The 50 immune-related DEGs were obtained between the T1DM and normal samples. Then, the 50 immune-related DEGs were further screened to obtain the 5 hub genes. CIBERSORT analysis revealed that the distribution of plasma cells, resting mast cells, resting NK cells and neutrophils had significant difference between T1DM and normal samples. Natural cytotoxicity triggering receptor 3 (NCR3) was significantly related to the activated NK cells, M0 macrophages, monocytes, resting NK cells, and resting memory CD4+ T cells. Moreover, tumor necrosis factor (TNF) was significantly associated with naive B cell and naive CD4+ T cell. NCR3 [Area under curve (AUC) = 0.918] possessed a higher accuracy than TNF (AUC = 0.763) in diagnosis of T1DM. CONCLUSIONS: The immune-related genes (NCR3 and TNF) and immune cells (NK cells) may play a vital regulatory role in the occurrence and development of T1DM, which possibly provide new ideas and potential targets for the immunotherapy of diabetes mellitus (DM).

Antinociceptive and Anti-Inflammatory Properties of Cannabidiol Alone and in Combination with Standardized Bioflavonoid Composition.

Symptom-alleviating therapies for osteoarthritis (OA) management are inadequate. Long-term application of first-line treatments, such as nonsteroidal anti-inflammatory drugs, is limited due to associated side effects. We believe that a combination of traditionally used botanical extracts, which have diverse active components that target multiple inflammatory pathways, may provide a safe and efficacious alternative to address the multifactorial nature of OA. Recently, cannabidiol (CBD), the major nonpsychoactive component of the hemp plant, has gained renewed global attention for its pharmacological actions. It has shown promise in reducing pain and inflammation in preclinical models of arthritis. In this study, widely employed inflammatory and noninflammatory animal pain models, such as the hot plate test, visceral pain model (writhing test), and carrageenan-induced rat paw edema model, were utilized to evaluate the antinociceptive and anti-inflammatory activity of CBD alone and in combination with standardized bioflavonoid compositions. CBD was tested at 5, 10, 20, and 40 mg/kg orally and at 5% topically. Administered alone, CBD produced dose-correlated, statistically significant pain inhibition in all the models. Enhanced performance in pain and inflammation reduction was observed when CBD was orally administered in complex with the bioflavonoid compositions. Data from this study show that for clinically meaningful efficacy against OA, CBD may have to be delivered in higher dosage or formulated with other medicinal plants with similar activities.

TERT promoter regulating melittin expression induces apoptosis and G0/G1 cell cycle arrest in esophageal carcinoma cells.

Esophageal squamous cell carcinoma accounts for a large proportion of cancer-associated mortalities in both men and women. Melittin is the major active component of bee venom, which has been reported to possess anti-inflammatory, antibacterial and anti-cancer properties. The aim of the present study was to construct a tumor targeted recombinant plasmid [pc-telomerase reverse transcriptase (TERT)-melittin] containing a human TERT promoter followed by a melittin coding sequence and to explore the effects of this plasmid in esophageal cell carcinoma and investigate preliminarily the underlying mechanisms of this effect. TE1 cells were transfected with pcTERT-melittin and the resulting apoptosis was subsequently examined. The viability of TE1 cells transfected with pcTERT-melittin was measured using a Cell Counting Kit-8 assay, which indicated inhibited proliferation. The disruption of mitochondrial membranes and the concomitant production of reactive oxygen species demonstrated an inducible apoptotic effect of melittin in TE1 cells. Apoptotic cells were also counted using an Annexin V-FITC and PI double-staining assay. The upregulation of cleaved caspase-9, cleaved caspase-3, Bax and poly(ADP-ribose) polymerase 1 in pcTERT-melittin transfected TE1 cells, suggested that pcTERT-melittin-induced apoptosis was associated with the mitochondrial pathway. TE1 cells were also arrested in the G0/G1 phase when transfected with pcTERT-melittin, followed by the decline of CDK4, CDK6 and cyclin D1 expression levels. As cell invasion and metastasis are common in patients with esophageal cancer, a cell migration assay was conducted and it was found that pcTERT-melittin transfection reduced the migratory and invasive abilities of TE1 cells. The findings of the present study demonstrated that pcTERT-melittin may induce apoptosis of esophageal carcinoma cells and inhibit tumor metastasis.

MKP-5 Relieves Lipotoxicity-Induced Islet ß-Cell Dysfunction and Apoptosis via Regulation of Autophagy.

Mitogen-activated protein kinase phosphatase-5 (MKP-5) is a regulator of extracellular signaling that is known to regulate lipid metabolism. In this study, we found that obesity caused by a high-fat diet (HFD) decreased the expression of MKP-5 in the pancreas and primary islet cells derived from mice. Then, we further investigated the role of MKP-5 in the protection of islet cells from lipotoxicity by modulating MKP-5 expression. As a critical inducer of lipotoxicity, palmitic acid (PA) was used to treat islet ß-cells. We found that MKP-5 overexpression restored PA-mediated autophagy inhibition in Rin-m5f cells and protected these cells from PA-induced apoptosis and dysfunction. Consistently, a lack of MKP-5 aggravated the adverse effects of lipotoxicity. Islet cells from HFD-fed mice were infected using recombinant adenovirus expressing MKP-5 (Ad-MKP-5), and we found that Ad-MKP-5 was able to alleviate HFD-induced apoptotic protein activation and relieve the HFD-mediated inhibition of functional proteins. Notably, HFD-mediated impairments in autophagic flux were restored by Ad-MKP-5 transduction. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) was used to treat Rin-m5f cells, confirming that the MKP-5 overexpression suppressed apoptosis, dysfunction, inflammatory response, and oxidative stress induced by PA via improving autophagic signaling. Lastly, employing c-Jun amino-terminal kinas (JNK), P38, or extracellular-regulated kinase (ERK) inhibitors, we established that the JNK and P38 MAPK pathways were involved in the MKP-5-mediated apoptosis, dysfunction, and autophagic inhibition observed in islet ß cells in response to lipotoxicity.

Efficacy of Acupuncture at the Sphenopalatine Ganglion in the Treatment of Persistent Allergic Rhinitis.

Objective: The aim of this research was to explore the hypothesis that acupuncture at the sphenopalatine ganglion (SPG), a new a new method of acupuncture, would be more efficacious and safe than traditional acupuncture in the treatment of persistent allergic rhinitis (PAR). Materials and Methods: For this study, 120 patients with PAR were randomly assigned to SPG acupuncture, traditional acupuncture (Yingxiang [LI 20], Hegu [LI 4], and Yintang [Ex-HN 3]), or drug treatment (budesonide nasal spray). Efficacy was assessed by using single symptoms, including sneezing, rhinorrhea, nasal obstruction and nasal itch, a total nasal symptoms score (TNSS), and a Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) before treatment, the day treatment ended, and 4-, 8-, 12-weeks later, respectively. Results: Four weeks after treatment ended, the effectiveness rate in the SPG-acupuncture group was superior to that of the traditional-acupuncture group (P = 0.033) but was still lower than that of the drug-treatment group (P = 0.039), with mean effectiveness rates of 69.70%, 44.44%, and 71.43%, respectively. However, these rates gradually decreased in each group during weeks 8 through 16. Moreover, statistically significant improvements in TNSS', and reductions in nasal congestion and sneezing symptoms were observed in the SPG-acupuncture group, compared with those in the traditional-acupuncture group as early as the day treatment ended and this continued throughout the observation period (P < 0.05). However, the improvement did not continue for sneezing, during weeks 8 through weeks 12 after treatment ended. The RQLQ of the SPG-acupuncture group was lower than that of the traditional-acupuncture group at week 12; however, there were no differences at weeks 8 and 16. Conclusions: The data generated by this study confirmed that acupuncture at the SPG alleviated the symptoms of PAR rapidly and safely, especially nasal obstruction, and improved the patients' life quality. These results were worthy of clinical promotion.

The Role of MKP-5 in Adipocyte-Macrophage Interactions during Obesity.

OBJECTIVE: In obese individuals, chronic low-grade inflammation resulting from adipocyte-macrophage interactions is a major cause of adipose tissue dysfunction and metabolic disease. This study investigated the role of MAP kinase phosphatase-5 (MKP-5) in obesity-induced inflammation during macrophage and adipocyte interactions. METHODS: High-fat diet-induced obese mice were used to explore the role of MKP-5 in obesity-induced adipose tissue inflammation. Macrophage polarization was determined by inflammatory cytokine expression in MKP-5-overexpressed or -silenced Raw264.7 cells exposed to palmitate (PA) or M1/M2 macrophage inducers. To uncover the role of MKP-5 during macrophage-adipocyte interactions, a coculture system composed of differentiated 3T3-L1 and Raw264.7 cells was employed. MAPK inhibitors were used to investigate the involvement of MAPK signaling. RESULTS: Increased MKP-5 expression was observed in adipose stromal vascular cells (SVCs) of obese mice. In Raw264.7 cells, MKP-5 promoted the switching of M1 macrophages to an M2 phenotype. Notably, MKP-5 reduced inflammation during the interaction of macrophages and adipocytes. MKP-5 overexpression in primary SVCs attenuated the expression of inflammatory mediators and increased the number of obesity-induced adipose tissue macrophages. MKP-5 suppressed PA-induced inflammation through the inactivation of P38, JNK, and ERK MAPKs. CONCLUSIONS: MKP-5 promotes macrophages to switch from the M1 to the M2 phenotype and is an inflammatory inhibitor involved in obesity-induced adipose tissue inflammation and PA-triggered macrophage inflammation via the P38, JNK, and ERK MAPK pathways. MKP-5 may be developed into a potential therapeutic target for obesity-related diseases, including type 2 diabetes mellitus and insulin resistance.

The protective role of the MKP-5-JNK/P38 pathway in glucolipotoxicity-induced islet ß-cell dysfunction and apoptosis.

Hyperglycemia and hyperlipidemia (glycolipotoxicity)-triggered islet ß-cell dysfunction is known to drive the progression of obesity-related type 2 diabetes, however the underlying mechanisms have not been clearly elucidated. The current study aimed to investigate the role of mitogen-activated protein kinase phosphatase 5 (MKP-5) in islet cells under glucolipotoxic conditions. Using gene overexpression and knockdown approaches, we demonstrated that MKP-5 could alleviate glucolipotoxicity-induced apoptosis via the endoplasmic reticulum (ER) stress and mitochondrial apoptosis pathways owing to the altered regulation of caspase family members and ER stress-related molecules in MIN6 and primary islet cells. Overexpression of MKP-5 reversed the glucose and palmitic acid (GP)-induced impairment of insulin secretion as well as the abnormal decreases in the expression of islet functional genes, thereby maintaining the normal insulin secretory functionality, whereas the absence of MKP-5 aggravated islet cell dysfunction. In parallel, the production of ROS and increased inflammation-associated genes in response to GP were also reduced upon MKP-5 overexpression. Further, inhibition of JNK or P38 MAPK pathways resisted to glucolipotoxicity observed in MKP-5 knockdown MIN6 cells. These findings indicate that MKP-5 is an important mediator for glucolipotoxicity-induced islet cell dysfunction and apoptosis, with JNK and P38 as the critical downstream pathways.

Morus alba, a Medicinal Plant for Appetite Suppression and Weight Loss.

The prevalence of obesity is expanding rapidly worldwide, making the disease a global burden with limited treatment options. The current obesity drug development trends suggest the possibility of reducing weight and reverse metabolic disturbances of obesity by controlling appetite. In this study, we screened more than 8000 plants from our plant library for the cannabinoid (CB1) receptor antagonists and identified Morus alba as a lead medicinal plant. Kuwanon G and Albanin G were isolated and identified from root-barks of Morus alba with 92% and 96% CB1 receptor ligand binding inhibitory activity, respectively. The bioflavonoid standardized extract was tested in the acute food intake study in rats at oral doses of 250 and 500 mg/kg for its appetite suppression activity. Diet-induced obesity in the C57BL/6J mice was used to evaluate the long-term food intake reduction activity and effect on the weight loss administered orally at 250 and 500 mg/kg for 7 weeks. Statistically significant and dose-dependent reduction in food intake was observed in both acute and long-term studies for the extract. Food intake reductions of 58.6% and 44.8% at 250 mg/kg and 50.1% and 44.3% at 500 mg/kg were observed at 1 and 2 h postfood provision, respectively. A 20% reduction in daily calorie intake was observed in the long-term study. Obese mice treated with the high dose of Morus root-bark extract showed 10.4 g (22.5%) and 7.1 g (16.5%) loss in body weight compared with the vehicle-treated obese animals (at week 7) and baseline, respectively. Statistically significant reductions in biochemical markers and visceral fat deposit were also observed. These results demonstrated that Morus alba extracts enriched in Kuwanon G, and Albanin G could be used alone to control appetite, manage body weight, and improve metabolic syndromes.

Postsurgical Evaluation of Secondary Nephrogenic Hyperparathyroidism.

Parathyroidectomy is useful for the treatment of secondary hyperparathyroidism (SHPT) caused by chronic renal failure. The following three types of parathyroidectomy can be performed: subtotal parathyroidectomy, total parathyroidectomy and total parathyroidectomy plus autologous transplantation (tPTX+AT). Each of the three types of surgery has advantages and disadvantages. The present study retrospectively analyzed the efficacy of tPTX+AT for the treatment of SHPT over 1 year. Thirty-seven patients who were diagnosed with secondary nephrogenic hyperparathyroidism and treated with tPTX+AT were selected between September 2014 and October 2016 and followed up for 1 year. Their average age was 66.5±46.0 years, and the average time of dialysis was 48.1±8.2 months. The patients' conditions, including the levels of intact parathyroid hormone (iPTH) and bone metabolism, were compared preoperatively and 1 and 7 days and 1, 3, 6 and 12 months after surgery. In addition, the postoperative complications, pathological data, SHPT recurrence and prognosis were examined. The results showed that the postoperative level of ostalgia and cutaneous pruritus significantly decreased in the patients. An inspection of the parathyroid tissues during the operation confirmed the presence of parathyroid gland hyperplasia with no carcinoma detected. Three patients with hoarseness recovered within 1 month, and 1 patient with unilateral recurrent laryngeal nerve injury improved after 6 months of voice training. Compared to the preoperative condition, the postoperative serum iPTH, serum calcium and serum phosphate levels were significantly decreased (P<0.001), and these differences remained significant 12 months after surgery. Compared to the preoperative condition, the alkaline phosphatase (ALP) concentration was decreased on postoperative day 1 (P<0.05), but no differences were observed on day 7 or at 1 month (P>0.05). The ALP levels continuously decreased at 3, 6 and 12 months (P<0.01). In conclusion, tPTX+AT significantly improves the quality of life and serum biomarker levels of these patients. The convenient surgical removal of the hyperplastic parathyroid gland for postoperative recurrence supports tPTX+AT as the recommended treatment for relevant patients.