Progress in controlling the transmission of schistosome parasites in Southern Ethiopia: the Geshiyaro Project in the Wolaita Zone.

BACKGROUND: This paper describes changes in the prevalence and intensity of schistosome parasite infections in a project integrating mass drug administration (MDA), water, sanitation, and hygiene (WaSH), and behavioral change interventions. METHODS: The Geshiyaro Project comprises three intervention arms. Arm 1 is subdivided into "Arm 1 pilot" (one district) and Arm 1 (four other districts), both receiving integrated community-wide MDA with intensive WaSH interventions. Arm 2 involves 17 districts with community-wide MDA interventions, while Arm 3 serves as a control with school-based MDA interventions in three districts. A total of 150 individuals, stratified by age group, were randomly selected from each of the 45 sentinel sites. Arm sizes were 584 (Arm 1 pilot), 1636 (Arm 1), 2203 (Arm 2), and 2238 (Arm 3). Statistical tests were employed to compare infection prevalence and intensity across the different arms. RESULTS: The prevalence of schistosome parasite infection ranged from 0% to 2.6% and from 1.7% to 25.7% across districts, employing the Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) diagnostics, respectively. The mean infection intensity level showed no marked difference between baseline and follow-up surveys when measured by KK, except in Arm 2 (t = 6.89, P < 0.0001). Infection prevalence decreased significantly in Arm 1 (t = 8.62, P < 0.0001), Arm 2 (t = 6.94, P < 0.0001), and Arm 3 (t = 8.83, P < 0.0001), but not in Arm 1 pilot (t = 1.69, P = 0.09) by POC-CCA, when trace was considered positive. The decrease was significant only in Arm 1 (t = 3.28, P = 0.0001) and Arm 2 (t = 7.62, P < 0.0001) when the trace was considered negative in POC-CCA. Arm 2 demonstrated a significant difference in difference (DID) compared to the control group, Arm 3, regardless of whether trace in POC-CCA was considered positive (DID = 3.9%, df = 8780, P = 0.025) or negative (DID = -5.2, df = 8780, P = 0.0004). CONCLUSIONS: The prevalence of schistosomiasis was low when employing the KK diagnostic but moderate in some locations by the POC-CCA diagnostic. The infection level had decreased across all arms of the Geshiyaro study at mid-term of the 7-year project, but further efforts are needed to reduce the rate of parasite transmission based on the POC-CCA diagnostic scores.

A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. METHODS: We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. RESULTS: C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Besides, C3a enhanced IL-1ß activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. CONCLUSION: Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.

Antidiabetic Effect of Urolithin A in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Glucose Intolerance.

Diabetes is caused by abnormal glucose metabolism, and muscle, the largest tissue in the human body, is largely involved. Urolithin A (UroA) is a major intestinal and microbial metabolite of ellagic acid and ellagitannins and is found in fruits such as strawberry and pomegranate. In this present study, we investigated the antidiabetic effects of UroA in L6 myotubes and in KK-Ay/Ta, a mouse model of type 2 diabetes (T2D). UroA treatment elevated the glucose uptake (GU) of L6 myotubes in the absence of insulin. This elevation in GU by UroA treatment was partially inhibited by the concurrent addition of LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K) which activates Akt (PKB: protein kinase B) or Compound C, an inhibitor of 5'-adenosine monophosphate-activated protein kinase (AMPK). Moreover, UroA was found to activate both pathways of Akt and AMPK, and then to promote translocation of glucose transporter 4 (GLUT4) from the cytosol to the plasma membrane in L6 myotubes. Based on these in vitro findings, an intraperitoneal glucose tolerance test (IPGTT) was performed after the oral administration of UroA for 3 weeks to KK-Ay/Ta mice with glucose intolerance. UroA was demonstrated to alleviate glucose intolerance. These results suggest that UroA is a biofactor with antihyperglycemic effects in the T2D state.

Effects of salt supplementation in uninephrectomized KK-Ay mice: Examining the potential of a diabetic kidney disease model.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Although current therapeutic strategies for DKD, including sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists, have shown some degree of efficacy, they have failed to completely halt the progression of DKD to ESRD owing to the complexity of DKD pathogenesis. Elucidating the pathophysiological mechanism of DKD is essential for the development of novel therapeutic strategies. In this study, we investigated the pathophysiological characteristics of uninephrectomized (UNx) KK-Ay mice and examined the effects of salt supplementation on the acceleration of renal injury in these mice. UNx KK-Ay mice exhibited pathophysiological renal abnormalities with glomerular and tubulointerstitial fibrosis. Additionally, salt supplementation exacerbated renal injury, particularly tubular injury. These results suggest that UNx KK-Ay mice are useful models for advanced DKD and that salt exacerbates tubular damage in DKD.

Increase in ENHANCER OF SHOOT REGENERATION2 expression by treatment with strigolactone-related inhibitors and kinetin during adventitious shoot formation in ipecac.

KEY MESSAGE: Increase of ENHANCER OF SHOOT REGENERATION 2 expression was consistent to treatment with kinetin, TIS108, and KK094 in adventitious shoot formation of ipecac. Unlike many plant species, ipecac (Carapichea ipecacuanha (Brot.) L. Andersson) can form adventitious shoots in tissue culture without cytokinin (CK) treatment. Strigolactone (SL) biosynthesis and signaling inhibitors stimulate adventitious shoot formation in ipecac, suggesting their potential use as novel growth regulators in plant tissue culture, but the molecular mechanism of their action is unclear. In this study, we compared the effects of SL-related inhibitors (TIS108 and KK094) and CKs (2iP, tZ, and kinetin) on adventitious shoot formation in ipecac. Exogenously applied SL-related inhibitors and CKs stimulated adventitious shoot formation. Combinations of SL-related inhibitors and kinetin also promoted adventitious shoot formation, but without additive effects. We also analyzed the expression of CK biosynthesis genes in ipecac. TIS108 increased the expression of the ipecac homolog of ISOPENTENYL TRANSFERASE 3 (CiIPT3) but decreased that of LONELY GUY 7 homolog (CiLOG7), presumably resulting in no change in 2iP-type CK levels. KK094 and kinetin increased CiLOG7 expression, elevating 2iP-type CK levels. Among pluripotency- and meristem-related genes, TIS108, KK094, and kinetin consistently increased the expression of ENHANCER OF SHOOT REGENERATION 2 homolog (CiESR2), which has a key role in shoot regeneration, in the internodal segment region that formed adventitious shoots. We propose that CiESR2 might be a key stimulator of adventitious shoot formation in ipecac.

The association of epidermal growth factor variant with oral squamous cell carcinoma.

In this study, our aim was to investigate the epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) gene polymorphisms in oral squamous cell carcinoma (OSCC) patients and non-OSCC healthy controls. This case-control study comprised 89 OSCC and 107 healthy controls by using polymerase chain reaction (PCR) and restriction fragment length polymorphism methods, the genotypes for EGF + 61 A > G (rs4444903) and EGFR R497K (rs2227983) were analyzed. According to the EGF + 61 A > G genotype distribution, individuals with the GG genotype were more prevalent in the OSCC group when compared to the healthy controls. But the AA genotype frequency was significantly higher in the healthy control group. The frequency of G allele carriers was 2.3 times higher than A allele carriers in OSCC patients (p < .001). For the EGFR R497K genotype, there was no significant difference between the OSCC and healthy control groups. Regarding the study results, the G allele of EGF + 61 A > G polymorphism was associated with OSCC. Larger populations and functional investigations should be used to explore the nature of the interaction between EGF and OSCC.

Delving into the reducing effects of the GABAB positive allosteric modulator, KK-92A, on alcohol-related behaviors in rats.

Recent studies have demonstrated the ability of the positive allosteric modulator (PAM) of the GABAB receptor (GABAB PAM), KK-92A, to suppress operant alcohol self-administration and reinstatement of alcohol seeking in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to scrutinize the suppressing effects of KK-92A on alcohol-related behaviors; to this end, four separate experiments were conducted to address just as many new research questions, some of which bear translational value. Experiment 1 found that 7-day treatment with KK-92A (0, 5, 10, and 20 mg/kg, intraperitoneally [i.p.]) effectively reduced alcohol intake in male sP rats exposed to the home-cage 2-bottle "alcohol (10% v/v) vs. water" choice regimen with 1 hour/day limited access, extending to excessive alcohol drinking the ability of KK-92A to suppress operant alcohol self-administration. Experiment 2 demonstrated that the ability of KK-92A to reduce lever-responding for alcohol was maintained also after acute, intragastric treatment (0, 20, and 40 mg/kg) in female sP rats trained to lever-respond for 15% (v/v) alcohol under the fixed ratio 5 schedule of reinforcement. In Experiment 3, acutely administered KK-92A (0, 5, 10, and 20 mg/kg, i.p.) dampened alcohol-seeking behavior in female sP rats exposed to a single session under the extinction responding schedule. Experiment 4 used a taste reactivity test to demonstrate that acute treatment with KK-92A (0 and 20 mg/kg, i.p.) did not alter either hedonic or aversive reactions to a 15% (v/v) alcohol solution in male sP rats, ruling out that KK-92A-induced reduction of alcohol drinking and self-administration could be due to alterations in alcohol palatability. Together, these results enhance the behavioral pharmacological profile of KK-92A and further strengthen the notion that GABAB PAMs may represent a novel class of ligands with therapeutic potential for treating alcohol use disorder.

In Vitro and In Vivo Antidiabetic Effects of Acidic Polysaccharides Extracted from Seaweeds.

We evaluated the α-glucosidase inhibitory activity of acidic polysaccharides (APs) extracted from seaweeds in vitro and their antidiabetic effects in KK-Ay mice. The α-glucosidase inhibitory activity of APs was differed among various seaweed species. Some APs showed higher inhibitory activity in the high-molecular-weight range, whereas others showed higher inhibitory activity in the low-molecular-weight range. Mice were fed low-molecular-weight APs from hijiki (LMWAPsH), which showed higher α-glucosidase inhibitory activity. Fasting blood glucose and HbA1c levels were significantly lower in the LMWAPsH group than in the control group (p<0.01). The calculated homeostasis model assessment-insulin resistance in the LMWAPsH group was significantly lower than that in the control group (p<0.05). These results suggest that α-glucosidase inhibitory activity differ among APs from different seaweed species, and each have an optimum molecular-weight range, and that LMWAPsH prevents the hyperglycemia in KK-Ay mice.

Targeting KK-LC-1 inhibits malignant biological behaviors of triple-negative breast cancer.

BACKGROUND: Cancer/testis antigens (CTAs) participate in the regulation of malignant biological behaviors in breast cancer. However, the function and mechanism of KK-LC-1, a member of the CTA family, in breast cancer are still unclear. METHODS: Bioinformatic tools, immunohistochemistry, and western blotting were utilized to detect the expression of KK-LC-1 in breast cancer and to explore the prognostic effect of KK-LC-1 expression in breast cancer patients. Cell function assays, animal assays, and next-generation sequencing were utilized to explore the function and mechanism of KK-LC-1 in the malignant biological behaviors of triple-negative breast cancer. Small molecular compounds targeting KK-LC-1 were also screened and drug susceptibility testing was performed. RESULTS: KK-LC-1 was significantly highly expressed in triple-negative breast cancer tissues than in normal breast tissues. KK-LC-1 high expression was related to poor survival outcomes in patients with breast cancer. In vitro studies suggested that KK-LC-1 silencing can inhibit triple-negative breast cancer cell proliferation, invasion, migration, and scratch healing ability, increase cell apoptosis ratio, and arrest the cell cycle in the G0-G1 phase. In vivo studies have suggested that KK-LC-1 silencing decreases tumor weight and volume in nude mice. Results showed that KK-CL-1 can regulate the malignant biological behaviors of triple-negative breast cancer via the MAL2/MUC1-C/PI3K/AKT/mTOR pathway. The small-molecule compound Z839878730 had excellent KK-LC-1 targeting ability and cancer cell killing ability. The EC50 value was 9.7 µM for MDA-MB-231 cells and 13.67 µM for MDA-MB-468 cells. Besides, Z839878730 has little tumor-killing effect on human normal mammary epithelial cells MCF10A and can inhibit the malignant biological behaviors of triple-negative breast cancer cells by MAL2/MUC1-C/PI3K/AKT/mTOR pathway. CONCLUSIONS: Our findings suggest that KK-LC-1 may serve as a novel therapeutic target for triple-negative breast cancer. Z839878730, which targets KK-LC-1, presents a new path for breast cancer clinical treatment.

γ-Linolenic Acid-Rich Oil- and Fish Oil-Induced Alterations of Hepatic Lipogenesis, Fatty Acid Oxidation, and Adipose Tissue mRNA Expression in Obese KK-A y Mice.

The physiological activity of γ-linolenic acid (GLA)-rich evening primrose oil and eicosapentaenoic and doxosahexaenoic acids-rich fish oil, which affect hepatic fatty acid oxidation and synthesis, and adipose tissue mRNA expression were compared in diabetic obese KK-A y mice. The mice were fed diets containing 100 g/kg of either palm oil (saturated fat), GLA oil, or fish oil for 21 days. These oils, compared with palm oil, greatly increased the activity and mRNA levels of hepatic fatty acid oxidation enzymes. These oils also increased the carnitine concentrations and mRNA levels of carnitine transporter (solute carrier family 22, member 5) in the liver. In general, these effects were comparable between GLA and fish oils. In contrast, GLA and fish oils, compared with palm oil, reduced the activity and mRNA levels of the proteins related to hepatic lipogenesis, except for those of malic enzyme. The reducing effect was stronger for fish oil than for GLA oil. These changes were accompanied by reductions in the triacylglycerol levels in the serum and liver. The reduction in the liver was stronger for fish oil than for GLA oil. These oils also reduced epididymal adipose tissue weight accompanied by a reduction in the mRNA levels of several proteins that regulate adipocyte functions; these effects were stronger for fish oil than for GLA oil. These oils were also effective in reducing serum glucose levels. Therefore, both fish oil and GLA-rich oil were effective at ameliorating metabolic disorders related to obesity and diabetes mellitus.

A Dendrimer Peptide (KK2DP7) Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy.

The clinical efficacy of personalized cancer vaccines still needs to be improved due to their insufficient immune effect. The development of innovative adjuvants and lymph node-targeted delivery systems is the key to improving the clinical efficacy of personalized vaccines. However, there is still a lack of an adjuvant delivery system that is simple in preparation and capable of mass production and integrates adjuvant and lymph node targeted delivery functions. Here, this work reports that a simple dendrimer polypeptide (KK2DP7) nanoparticle enhances the immune efficacy of an OVA/neoantigen-based vaccine. Due to its multiple functions as a delivery vehicle, immune adjuvant, and facilitator of dendritic cell migration, KK2DP7 efficiently increases the efficiency of antigen uptake and cross-presentation by antigen-presenting cells (APCs) and delivers antigens to lymph nodes via APCs. Strikingly, the antitumor effect of KK2DP7/OVA is superior to that of commonly used adjuvants such as poly(I:C), CpG, and aluminum adjuvant combined with OVA. Furthermore, KK2DP7/OVA combined with anti-PD-1 antibody is able to prevent tumor recurrence in a postoperative recurrent tumor model. Thus, KK2DP7-based cancer vaccines alone or in combination with immune checkpoint blockade therapies to treat tumors or postoperative tumor recurrence are a powerful strategy to enhance antitumor immunity.

Compound Danshen Dripping Pills moderate intestinal flora and the TLR4/MyD88/NF-κB signaling pathway in alleviating cognitive dysfunction in type 2 diabetic KK-Ay mice.

BACKGROUD: Bidirectional communications between the gut microbiota and the brain may play a critical role in diabetes-related cognitive impairment. Compound Danshen Dripping Pills (CDDP) treatment has shown remarkable improvement in cognitive impairment in people with type 2 diabetes mellitus (T2DM) in clinical settings, but the underlying mechanisms remain unknown. PURPOSE: An extensive detailed strategy via in vivo functional experiments, transcriptomics, metabolomics, and network pharmacology was adopted to investigate the CDDP-treatment mechanism in diabetic cognitive dysfunction. METHODS: For 12 weeks, KK-Ay mice, a spontaneous T2DM model, were intragastrically administered various doses of CDDP solution or an equivalent volume of water, and the nootropic drug piracetam was orally administered as a positive control. At the 12th week, cognition was assessed using Morris water maze tests and brain magnetic resonance imaging (MRI). Furthermore, transcriptomics, metabolomics, and network pharmacology analyses were applied to reveal novel molecular mechanisms of CDDP-treatment in diabetic cognitive dysfunction of KK-Ay mice, which were then validated using quantitative real-time polymerase chain reaction and Western blot. RESULTS: Here we verified that CDDP can suppress inflammatory response and alleviate the cognitive dysfunction in KK-Ay mice. Also, as demonstrated by 16S rRNA sequencing and short-chain fatty acids (SCFAs) analysis, CDDP attenuated intestinal flora disorder as well as increases of metabolites including butyric acid, hexanoic acid, and isohexic acid. Given the integrated analyses of network pharmacology, transcriptomic, metabolomic data, and molecular biology, the TLR4/MyD88/NF-κB signaling pathway was activated in diabetes, which could be reversed by CDDP. CONCLUSIONS: Our findings demonstrate that CDDP restructures the gut microbiota composition and increased the intestinal SCFAs in KK-Ay mice, which might inhibit neuroinflammation, and thus improve diabetic mice cognitive disorder.

Stimulation of glucose uptake by glycosides from Alectra parasitica subsp. chitrakutensis (M.A. Rau) K.K. Khanna & An. Kumar: An in-vitro study of TNF-α induced insulin resistance in L6 myoblasts.

Alectra parasitica subsp. chitrakutensis (M.A. Rau) K.K. Khanna & An. Kumar (Orobanchaceae) is a parasitic plant indigenous to India. Locally, the plant is known as 'Midaki and Nirgundikand'. It is used to treat fever, piles, cardiovascular disorders, and blood-borne non-infectious diseases by ethnic communities. The phytochemical investigation of A. parasitica subsp. chitrakutensis rhizome led to the isolation of azafrin (1), rehmaionoside-C (2), and mussaenoside (3). Compounds (2) and (3) are being reported for the first time from this plant. Compounds were evaluated for their intercellular glucose uptake activity in basal and insulin-TNF-α-stimulated L6 muscle cells. In particular, rehmaionoside C exhibited activity comparative to metformin, increasing uptake by basal- and insulin-TNF-α-stimulated cells by 4.88- and 3.90-fold and 5.04- and 4.04-fold. While azafrin and mussaenoside have produced 3.03- and 2.36-fold; 4.03- and 3.22-fold increase in intercellular glucose uptake. Compounds did not show toxicities in rat L6 myoblast cells. The study suggests that rehmaionoside-C from A. parasitica subsp. chitrakutensis might activate glucose uptake by insulin mimics and could be a nontoxic anti-diabetes lead for drug discovery.

Effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice / 中国药房

OBJECTIVE To investigate the effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice. METHODS KK-Ay mice were randomly divided into model group， metformin group （200 mg/kg） and A. sinensis polysaccharide high-dose， medium-dose and low-dose groups （400， 200 and 100 mg/kg）； C57BL/6J mice were included in blank group， with 8 mice in each group. Each group was given relevant medicine intragastrically or normal saline， once a day， for consecutive 4 weeks. After the final administration， the levels of fasting glucose， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C） and insulin （INS） were detected； the protein expressions of B-cell lymphoma 2 （Bcl-2）， cleaved- caspase-3， apoptosis signal-regulated kinase 1 （ASK1）， phosphorylated c-Jun N-terminal kinase （p-JNK）， phosphorylated inositol- requiring enzyme 1α （p-IRE1α） in myocardium， and apoptosis in cardiomyocytes were also detected. RESULTS Compared with model group， the fasting glucose， TC and LDL-C content， apoptotic rate of cardiomyocyte， protein expressions of p-JNK and p- IRE1α， ASK1， cleaved-caspase-3 were significantly lower in the metformin group and A. sinensis polysaccharide medium-dose， high-dose groups； INS level and relative expression of Bcl-2 protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS A. sinensis polysaccharide can improve the levels of blood glucose and blood lipid and inhibit cardiomyocyte apoptosis in diabetic KK-Ay mice， and the mechanism may be related to the inhibition of IRE1/ASK1/JNK signaling pathway.

Antibody functionalized intravascular devices combined with genetically engineered endothelial colony-forming cells for targeted drug delivery: A proof-of-concept study.

This study was designed to test the ability of ex vivo antibody-coated intravascular devices to capture genetically engineered pig endothelial colony-forming cells (ECFCs) as proof of concept for their potential for in vivo targeted drug delivery. Human α-calcitonin gene-related peptide (α-CGRP) was chosen as the therapeutic molecule as it is unsuitable for systemic administration due to its potent peripheral arterial vasodilatory effect and short half-life in blood, requiring local delivery to yield therapeutic benefit in a particular vascular bed. H-2Kk, a murine leukocyte surface antigen, served as the selection marker for genetically modified ECFCs. H-2Kk antibody was immobilized on electropolished cobalt-chromium (CC) discs, CC stents and ePTFE grafts through dopamine self-polymerization. The functionalized surface was integral and smooth, lacked or had significantly reduced chemical signals specific for substrates. Pig bone marrow-derived ECFCs transfected with a plasmid constructed for H-2Kk and α-CGRP expression produced H-2Kk on cell surface and biologically active α-CGRP in culture medium. H-2Kk antibody-coated substrates bound H-2Kk ECFCs but not control ECFCs in vitro. Bare or only dopamine-coated substrates did not bind H-2Kk ECFCs. These data suggest that implantation of antibody functionalized devices combined with injection of genetically modified ECFCs could be potentially applied for targeted drug delivery.

Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated. METHODS: In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells. RESULTS: The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis. CONCLUSIONS: In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.

Amycenone reduces excess body weight and attenuates hyperlipidaemia by inhibiting lipogenesis and promoting lipolysis and fatty acid ß-oxidation in KK-Ay obese diabetic mice.

Excess body weight and hyperlipidaemia cause severe health problems and have social implications. Amycenone is an active substance extracted from Yamabushitake mushrooms with no reports of its activity against excess body weight and hyperlipidaemia. This research clarifies the effects and mechanisms of action of amycenone on the inhibition of body weight excess and hyperlipidaemia attenuation using KK-Ay mice. Amycenone or water was administered to 8-week-old male KK-Ay mice by gavage for 8 weeks. Their body weight and food intake were recorded during the experiment. At the end of the experimental period, the mice were dissected, and blood samples, lipid metabolism-related organs and tissues were collected and stored for further analysis. Amycenone treatment suppressed body weight gain and improved serum levels of fasting blood glucose and non-esterified fatty acids. Additionally, serum and hepatic cholesterol and triacylglycerol levels were reduced after this treatment, whereas the phosphorylation levels of AMPK, PKA and HSL increased and the expression level of FAS decreased. The protein level of C/EBPß and gene expression level of Cpt1 were higher in the perirenal adipose tissue of amycenone-treated KK-Ay mice. Furthermore, amycenone phosphorylated AMPK, PKA and ACC, and PPARγ expression was lower in the mesenteric adipose tissue. The phosphorylation levels of AMPK, LKB1, PKA and ACC were also induced, and FAS expression level was reduced in the liver of the amycenone-treated group. Amycenone could reduce excess body weight and attenuate hyperlipidaemia in KK-Ay mice by inhibiting lipogenesis and promoting lipolysis through lipid metabolism pathway stimulation and fatty acid ß-oxidation acceleration.

Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1): A Promising Cancer Testis Antigen.

Cancer has always been a huge problem in the field of human health, and its early diagnosis and treatment are the key to solving this problem. Cancer testis antigens (CTAs) are a family of multifunctional proteins that are specifically expressed in male spermatozoa and tumor cells but not in healthy somatic cells. Studies have found that CTAs are involved in the occurrence and development of tumors, and some CTAs trigger immunogenicity, which suggests a possibility of tumor immunotherapy. The differential expression and function of CTAs in normal tissues and tumor cells can promote the screening of tumor markers and the development of new immunotherapies. This article introduces the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1), a new member of the CTA family, in different types of tumors and its role in immunotherapy.

Free Space Ground to Satellite Optical Communications Using Kramers-Kronig Transceiver in the Presence of Atmospheric Turbulence.

Coherent detection provides the optimum performance for free space optical (FSO) communication systems. However, such detection systems are expensive and require digital phase noise compensation. In this paper, the transmission performance of long-haul FSO system for ground-to-satellite communication based on a Kramers-Kronig (KK) transceiver is evaluated. KK transceivers utilize inexpensive direct detection receivers and the signal phase is retrieved from the received current using the well-known KK relations. KK transceivers are not sensitive to the laser phase noise and, hence, inexpensive lasers with large linewidths can be used at the transmitter. The transmission performance of coherent and KK transceivers is compared in various scenarios such as satellite-to-ground, satellite-to-satellite, and ground-to-satellite for weak, moderate, and strong turbulence. The results show that the transmission performance of a system based on the KK transceiver is comparable to that based on a coherent transceiver, but at a significantly lower system cost and complexity. It is shown that in the absence of turbulence, the coherent receiver has a ~3 dB performance advantage over the KK receiver. However, in the presence of strong turbulence, this performance advantage becomes negligible.

Phenotypic and genotypic changes in obesity and type 2 diabetes of male KK mice with aging.

Research into the prevention and treatment of age-related metabolic diseases are important in the present-day situation of the aging population. We propose that an elderly diabetic mouse model may be useful to such research as it exhibits deterioration of glucose and lipid metabolism. Although the KK mouse strain is commonly used as a model of moderate obesity and type 2 diabetes, the utility of this strain as an elderly obese and diabetic model mouse for research into aging remains unclear. The present study aimed to investigate age-related changes of glucose and lipid metabolism in male KK mice fed a standard chow diet. We demonstrate that 40 weeks KK mice exhibit age-related dysfunctions, such as development of insulin resistance associated with pancreatic islet hypertrophy and decreased lipolysis in white adipose tissue (WAT) compared with 15 weeks KK mice. However, aging does not appear to cause mitochondrial dysfunction of brown adipose tissue. Unexpectedly, hyperglycemia, potential glucose uptake in insulin-sensitive organs, hepatic lipid accumulation, hypertrophy of adipocytes, and inflammation in epididymal WAT did not worsen but rather compensated in 40 weeks KK mice. Our data indicate that the use of male KK mice as an elderly obese and diabetic mouse model has some limitations and in order to represent a useful elderly obese and diabetic animal model, it may be necessary to induce deterioration of glucose and lipid metabolism in KK mice through breeding with high-sucrose or high-fat diets.