Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Exploring Effect of Postdischarge Developmental Support Program on Preterm Infant Neurodevelopment and BDNF Gene DNA Methylation.

BACKGROUND: Although developmental supportive care is an effective approach to improve the long-term psychomotor and/or neurobehavioral function of preterm infants, very limited studies have focused on the impact of after-discharge developmental support. The underlying epigenetic changes are unclear. PURPOSE: This study aimed to explore the preliminary effect of an evidence-based Postdischarge Developmental Support Program (PDSP) on preterm infant neurodevelopment and underlying epigenetic changes, including brain-derived neurotrophic factor (BDNF) gene-related DNA methylation and expression. METHODS: In this randomized controlled pilot trial, the preterm infant-parent dyads were randomized into either the intervention group/PDSP group (n = 22) or the control group/usual care group (n = 22). The neurodevelopmental outcomes of preterm infants were measured by Ages & Stages Questionnaires. Urine BDNF concentration level was tested by the enzyme-linked immunosorbent assay. Infant saliva specimens were collected to analyze the methylation level of BDNF gene promoter I at pre- and postintervention test. RESULTS: After PDSP intervention, the total neurodevelopmental and the 5 domain scores of the PDSP group were all significantly higher than those of the control group ( P < .05). The BDNF levels decreased significantly only within control group ( P = .01). The difference in BDNF concentration and methylation levels between groups was not statistically significant. IMPLICATIONS FOR PRACTICE AND RESEARCH: Postdischarge Developmental Support Program may promote the neurodevelopment of preterm infants but has no effect on BDNF's expression and gene methylation level at 3 months of corrected age. The epigenetic mechanism of PDSP needs further study using a larger sample and longer follow-up.

Citrus-derived DHCP inhibits mitochondrial complex II to enhance TRAIL sensitivity via ROS-induced DR5 upregulation.

Heat-modified citrus pectin, a water-soluble indigestible polysaccharide fiber derived from citrus fruits and modified by temperature treatment, has been reported to exhibit anticancer effects. However, the bioactive fractions and their mechanisms remain unclear. In this current study, we isolated an active compound, trans-4,5-dihydroxy-2-cyclopentene-l-one (DHCP), from heat-treated citrus pectin, and found that is induces cell death in colon cancer cells via induction of mitochondrial ROS. On the molecular level, DHCP triggers ROS production by inhibiting the activity of succinate ubiquinone reductase (SQR) in mitochondrial complex II. Furthermore, cytotoxicity, apoptotic activity, and activation of caspase cascades were determined in HCT116 and HT-29 cell-based systems, the results indicated that DHCP enhances the sensitivity of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with DHCP-induced ROS accounting for the synergistic effect between DHCP and TRAIL. Furthermore, the combination of DHCP and TRAIL inhibits the growth of HCT116 and HT-29 xenografts synergistically. ROS significantly increases the expression of TRAIL death receptor 5 (DR5) via the p53 and C/EBP homologous protein pathways. Collectively, our findings indicate that DHCP has a favorable toxicity profile and is a new TRAIL sensitizer that shows promise in the development of pectin-based pharmaceuticals, nutraceuticals, and dietary agents aimed at combating human colon cancer.

Impact of COVID-19 pandemic on the epidemiology of STDs in China: based on the GM (1,1) model.

BACKGROUND: COVID-19 and Sexually Transmitted Diseases (STDs) are two very important diseases. However, relevant researches about how COVID-19 pandemic has impacted on the epidemiological trend of STDs are limited in China. This study aimed to analyze the impact of COVID-19 on STDs in China and proposed relevant recommendations to be used in bettering health. METHODS: The incidence of HIV infection, syphilis and gonorrhea in China from 2008 to 2020 were collected. Grey Model (1,1) were established to predict the incidence of STDs with the incidence data of these three STDs from 2013 to 2018 considering the impact of policies in China, respectively. We then calculated the predictive incidence of each STD in 2019, 2020 and 2021 by the established Model. And we estimated the extent of the impact of COVID-19 on the epidemiological changes of STDs by analyzing the difference between the absolute percentage error (APE) of the predictive incidence and actual rate in 2019 and 2020. RESULTS: The incidence of HIV infection and syphilis showed a trend of increase from 2008 to 2019 in China, but that for gonorrhea was fluctuant. Of note, the incidence of these three STDs decreased significantly in 2020 compared with that in 2019. The APE of HIV infection, syphilis and gonorrhea in 2020 (20.54%, 15.45% and 60.88%) were about 7 times, 4 times and 2 times of that in 2019 (2.94%, 4.07% and 30.41%). The incidence of HIV infection, syphilis and gonorrhea would be 5.77/100,000, 39.64/100,000 and 13.19/100,000 in 2021 based on our model. CONCLUSIONS: The epidemiological trend of STDs in China was significant influenced by COVID-19 pandemic. It is important to balance the control of COVID-19 and timely management of STDs during the COVID-19 epidemic to prevent or reduce the poor outcome among COVID-19 patients with STDs. New management strategies on STDs, such as leveraging social media, online medical care, rapid self-testing, timely diagnosis and treatment guarantee and balance of medical resources for STDs management should be adapted in the context of the long-term effects of COVID-19.

Family-based improvement for health literacy among the Yi nationality (FAMILY) in Liangshan: protocol of an open cohort stepped wedge cluster randomized controlled trial.

BACKGROUND: Improvement of health literacy constitutes a cornerstone to improving public health. However, the overall health literacy of Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) in the southwest Sichuan Province of China has kept extremely low for a long time. How to improve health literacy of the Yi nationality residents is key to be urgently solved. Notably, Family Branch System is a distinctive patrilineal bloodline organization of Yi nationality, which plays an important role in the daily life of Yi nationality. Meanwhile, Contracted Family Doctor Services is conducted in Liangshan Prefecture. Therefore, this study proposes an intervention model of health education based on Family Branch System and Contracted Family Doctor Services, which is a Family-based Improvement for Health Literacy among the Yi nationality (FAMILY) in Liangshan, when improving traditional Innovative Care for Chronic Conditions Framework (ICCC) framework. METHODS: An open cohort stepped wedge cluster randomized trial design is used to implement health literacy education interventions including project preparation, core group building, promotion within family branch and competition between family branches while using Contracted Family Doctor Services as control measure. The study will be conducted among Yi nationality residents in Meigu County and Yanyuan County, with health literacy level of residents as the primary outcome. Finally, mixed-effects model and causal inference method will be used to evaluate intervention effect. DISCUSSION: This study highlights family, using the unique Family Branch System and Contracted Family Doctor Services in Liangshan Prefecture to design intervention among improved ICCC framework, and combines the mixed-effects model with complier average causal effects (CACE) to estimate the intervention effect under non-compliance for the first time. Besides, other key technologies to be adopted include construction of electronic questionnaire quality control system, with quality control based on artificial intelligence. This trial contributes to exploring an effective way to improve health literacy of Yi nationality residents in Liangshan Prefecture, which will provide reference for other areas, especially poor areas, to improve residents' health literacy. TRIAL REGISTRATION: ISRCTN11299863 on June 1, 2022; https://www.isrctn.com/ .

Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice.

BACKGROUND: Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent. RESULTS: We demonstrated that tauroursodeoxycholic acid (TUDCA), a clinically available endoplasmic reticulum (ER) stress inhibitor, can promote B. pseudomallei clearance both in vivo and in vitro. In this study, we investigated the effects of TUDCA on the survival of melioidosis mice, and found that treatment with TUDCA significantly decreased intracellular survival of B. pseudomallei. Mechanistically, we found that B. pseudomallei induced apoptosis and activated IRE1 and PERK signaling ways of ER stress in RAW264.7 macrophages. TUDCA treatment could reduce B. pseudomallei-induced ER stress in vitro, and TUDCA is protective in vivo. CONCLUSION: Taken together, our study has demonstrated that B. pseudomallei infection results in ER stress-induced apoptosis, and TUDCA enhances the clearance of B. pseudomallei by inhibiting ER stress-induced apoptosis both in vivo and in vitro, suggesting that TUDCA could be used as a potentially alternative treatment for melioidosis.

Polysaccharide-Enriched Fraction from Amillariella Mellea Fruiting Body Improves Insulin Resistance.

Despite the edible fungus Amillariella mellea possessing a variety of biological activities, its effects on diabetes are still unclear. Polysaccharides are the main bioactive ingredients. In order to destroy the cell wall to obtain more polysaccharides, we used NaOH solution to extract Amillariella mellea fruiting bodies. The alkali extraction (AAMP) was identified as a polysaccharide-enriched fraction. Using type 2 diabetic rats induced by co-treatment of a high fat diet (HFD) and dexamethasone (DEX), we evaluated the hypoglycemic effects of AAMP. The results showed that oral administration of a high dose of AAMP markedly lowered fasting blood glucose, improving glucose intolerance and insulin resistance. AAMP also enhanced the level of LPL and the expressions of two critical lipases ATGL and HSL, leading to a decrease of serum triglyceride. In addition, AAMP specifically suppressed the expression of SREBP-1c, resulting in AAMP observably inhibiting lipid accumulation in the liver. These findings demonstrated that the improvement of AAMP on HFD/DEX-induced insulin resistance was correlated with its regulation of lipid metabolism. Our results indicated that AAMP could be a novel natural drug or health food used for the treatment of diabetes.

Novel polysaccharide binding to the N-terminal tail of galectin-3 is likely modulated by proline isomerization.

Interactions between galectins and polysaccharides are crucial to many biological processes, and yet these are some of the least understood, usually being limited to studies with small saccharides and short oligosaccharides. The present study is focused on human galectin-3 (Gal-3) interactions with a 60 kDa rhamnogalacturonan RG-I-4 that we use as a model to garner information as to how galectins interact with large polysaccharides, as well as to develop this agent as a therapeutic against human disease. Gal-3 is unique among galectins, because as the only chimera-type, it has a long N-terminal tail (NT) that has long puzzled investigators due to its dynamic, disordered nature and presence of numerous prolines. Here, we use 15N-1H heteronuclear single quantum coherence NMR spectroscopy to demonstrate that multiple sites on RG-I-4 provide epitopes for binding to three sites on 15N-labeled Gal-3, two within its carbohydrate recognition domain (CRD) and one at a novel site within the NT encompassing the first 40 residues that are highly conserved among all species of Gal-3. Moreover, strong binding of RG-I-4 to the Gal-3 NT occurs on a very slow time scale, suggesting that it may be mediated by cis-trans proline isomerization, a well-recognized modulator of many biological activities. The NT binding epitope within RG-I-4 appears to reside primarily in the side chains of the polysaccharide, some of which are galactans. Our results provide new insight into the role of the NT in Gal-3 function.

Increased expression of ESCO1 is correlated with poor patient survival and its role in human bladder cancer.

There is increasing evidence suggesting that establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) was involved in tumorigenesis. However, its role in bladder cancer remains unclear. In this study, we aimed to study the clinical correlation and biological significance of ESCO1 in bladder cancer. Our results showed that ESCO1 was significantly over-expressed in bladder cancer tissues compared with that in adjacent normal tissues. And, increased ESCO1 expression was significantly associated with higher grade (P < 0.001), higher tumor stage (P = 0.014), and multifocality (P = 0.042). Kaplan-Meier analysis and Cox proportional hazards model were performed to determine the prognostic significance of ESCO1, and the results showed that ESCO1 is a useful prognostic marker for bladder cancer patients. Moreover, we found that ESCO1 knockdown inhibited the growth, migration, and invasion of bladder cancer cells. In conclusion, our findings indicated that ESCO1 may play an important role in human bladder cancer, and ESCO1 might serve as a novel target and prognosis factor for human bladder cancer.

In vivo anticancer and immunomodulating activities of mannogalactoglucan-type polysaccharides from Lentinus edodes (Berkeley) Singer.

There is considerable interest in the potential of mushrooms in modulating the immune system and/or suppressing tumor growth. Among the studied bioactive compounds in mushrooms, polysaccharides are the most important. Nontoxic fungal polysaccharides have a more important role in immunomodulating and antitumor activities which are related to their effects to act of immune effecter cells such as lymphocytes, macrophages, dendritic cells, and natural killer cells involved in the innate and adaptive immunity. Two mannogalactoglucan-type polysaccharides (WPLE-N-2 and WPLE-A0.5-2), purified from the fruiting bodies of Lentinus edodes, were evaluated for their effects on the cellular immune response of Sarcoma 180 (S-180)-bearing mice. Mice were treated with 100 mg/kg body weight of the polysaccharides for 10 days. Significant tumor regressions of the polysaccharide groups' mice were observed compared to the control group. These polysaccharides could induce an increase in nitrite oxide (NO) production in peritoneal macrophages, significantly increase macrophage phagocytosis of tumor-bearing mice and augment concanavalin (ConA) and lipopolysaccharide (LPS)-induced splenocytes proliferation. Our results indicated that immunomodulating activity occurred through host mediation in response to lymphocyte proliferation, macrophage phagocytosis and induction of NO production while the antitumor activity occurred through direct cytotoxicity. Our findings suggest that mannogalactoglucan-type polysaccharides from L. edodes can be explored as novel potential immunostimulants. Our research provides essential data to a better understanding of L. edodes bioactive compounds, especially polysaccharides. Our results also confirm the key role of ß-linkages in the antitumor and immunomodulating effects of polysaccharides.

The role of tumor suppressor gene SOX11 in prostate cancer.

SOX genes play an important role in a number of developmental processes. The transcription factor SOX11 is one of the members of the SOX family emerging as important transcriptional regulators. The aim of this study was to investigate the role of SOX11 in prostate cancer (PCa) and its expression pattern and clinical significance. The gene expression of SOX11 in human PCa tissues compared with benign prostate hyperplasia (BPH) tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. SOX11 overexpression cell model was used to examine the role of SOX11 in cell growth and metastasis in vitro. The results showed that the positive rate of SOX11 staining was 16.67 % (10/60) in cases of prostatic carcinoma and 81.67 % (49/60) in cases of BPH, and the difference of SOX11 expression between PCa and BPH was statistically significant (P < 0.001). SOX11 mRNA level was lowly expressed in PCa cell lines compared to RWPE-1. SOX11 overexpression suppresses PCa cell migration and invasion. In conclusion, our findings demonstrate that SOX11 could suppress cell proliferation, migration, and invasion of PCa in vitro.

[Effect of urinary Tamm-horsfall protein concentration changes under centrifugation and its association with urolithiasis formation in rats].

OBJECTIVE: To explore the concentration changes of Tamm-Horsefall protein (THP) under centrifugation in rat urine and discuss its association with urolithiasis formation. METHODS: A total of 40 Wistar rats were divided randomly into 4 groups of flying with stone (A), flying without stone (B), stone without flying (C) and control (D). After centrifugation, the THP concentrations of each group were measured by enzyme-linked immunosorbent assay (ELISA). Then urinary system was dissected, stained with hematoxylin & eosin and observed under electron microscopy to examine the distribution and number of each section. The SPSS 13.0 software was used for data analyses. RESULTS: Group A showed significant difference in THP concentrations with groups C and D ( (11 ± 4) vs (15 ± 6), (17 ± 4) ng/ml, P = 0.037 and 0.005).No statistically significant difference existed between groups A and B ((11 ± 5) ng/ml, P = 0.998) or groups C and D (P = 0.422). Group B had significant difference in THP concentrations with groups D (P = 0.036). Regarding the number of stones in ureter, Group A had statistically significant difference with B (P = 0.029).However, there was no difference in the number of bladder stones.In kidney stones, there was significant difference (P = 0.029) on "+ +" rating. CONCLUSION: Centrifugation may reduce the urinary concentration of THP so as cause urolithiasis formation in rats.

Burkholderia pseudomallei BipD modulates host mitophagy to evade killing.

Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.

Effect of O antigen glycosyl isomerase gene mutation on biological property and pathogenicity of Burkholderia pseudomallei strain BPC006.

Burkholderia pseudomallei, an intracellular pathogen, is responsible for melioidosis, a zoonotic disease. Its pathogenesis involves several virulence factors, among which lipopolysaccharide (LPS) plays a crucial role. Our research reveals that the O antigen present within the LPS significantly regulates the host immune response. In a previous study, we obtained a B. pseudomallei mutant strain ΔwbiI. Here, the purification of LPS from ΔwbiI and a gas chromatography-mass spectrometry (GC-MS) analysis were conducted. The results confirmed the absence of specific sugar 6-deoxy-Talp, which is a typical component of the O antigen in the wild type B. pseudomallei. Our findings underscore the potent impact the O antigen exerts on the virulence of B. pseudomallei. The ΔwbiI strain displayed significantly increased invasiveness and cytotoxicity in vitro. This enhanced cytotoxicity seems to be related to the exposure of lipid A and an increased cell membrane hydrophobicity resulting from the deletion of the O antigen. Additionally, in mouse models, the ΔwbiI strain resulted in a heightened host lethality and an excessive inflammatory response in mice. These findings indicate that the O-antigenic polysaccharide moiety of B. pseudomallei plays a role in its pathogenicity in vitro and in vivo.

Improvements in skills and knowledge after a comprehensive ELISA teaching course for biotechnology undergraduates.

As a universal and extensively adopted technique, enzyme-linked immunosorbent assay (ELISA) can be used to detect and quantify small molecules in many applications both clinical and analytical. However, generally, students experiment mechanically using commercial ELISA kits according to the instructions and eventually produce a standard curve to calculate the concentration of the sample to be measured, cannot understand the critical factors and process of method establishment. This study systematically introduced undergraduates to using the pathogen-specific antigen and establishing an indirect ELISA method to detect the diagnostic target pathogen Burkholderia pseudomallei. This course aimed to develop the experimental skills of the students and improve their scientific research knowledge, which fully embody the organic combination of scientific research and teaching. Students independently selected the diagnostic antigen target of interest, obtained the antigen proteins using genetic engineering techniques, and established an ELISA method through a series of conditional optimization experiments. In addition, typical student-generated data, experimental methods, and a student feedback interpretation are presented in this study. Overall, the students were able to combine abstract knowledge with practice and understand the principles and applications of antigen-antibody interactions, thus enabling them to gain practical experience in molecular biology techniques, and learn how to use this principle to establish an ELISA method for detecting infectious diseases.

High-Temperature Chlorination of Nickel Oxide Using Calcium Chloride.

Attempts have been made to extract nickel from ores and nickel-containing wastes using the chlorination method. However, the use of gaseous chlorinating agents is limited due to their toxicity. High-temperature chlorination of nickel oxide using calcium chloride is analyzed in this study. The volatilization percentage is positively correlated to temperature and CaCl2 dosage and negatively correlated to oxygen partial pressure. The apparent activation energy is calculated to be 142.91 kJ/mol, between 1173 K and 1323 K, which suggests that the high-temperature chlorination of nickel oxide using calcium chloride is controlled by a chemical reaction.

Characterization of Burkholderia pseudomallei O antigens in different clinical strains.

O antigen is the major component of lipopolysaccharide LPS. The chemical structure of the O antigen determines the LPS serospecificity of the bacteria, and the diversity of O antigen is the basis for serotyping Burkholderia pseudomallei. In this study, structural elucidation of type B O antigen obtained from a clinical B. pseudomallei strain was conducted, and the effects of different types of LPS on macrophage differentiation were investigated. The O antigen was found to be composed of repeating units of [→4)-α-L-Rhap(1 â†’ 4)-α-L-Rhap(1→2)-α-L-Rhap(1 â†’ 2)-α-L-Rhap(1 â†’ 3)-α-L-Rhap(1 â†’ 3)-α-L-Rhap(1 â†’ 4)-α-L-Rhap(1 â†’ 6)-α-D-Galp(1→]n, where some of the →4)-α-L-Rhap(1 â†’ units were substituted at O-3 by ß-D-Xylp(1 â†’ residues, and minor →3)-α-L-Rhap(1 â†’ units were substituted at O-2 by ß-D-Xylp(1 â†’ residues. Meahwhile, the →6)-α-D-Galp(1 â†’ units were substituted at O-3 by α-D-Galp(1 â†’ residues. Furthermore, both type A and type B O antigens of B. pseudomallei could polarize macrophages toward the M1 phenotype, but the core oligosaccharides had no such activity. Therefore, we deduced that this polarization relies on the O antigen of LPS and might be related to the ability of B. pseudomallei to survive and replicate within macrophages. Thus, the characterization of different types of O antigen structural motifs is essential for further clarifying the persistence/survival mechanisms and inflammatory potential of B. pseudomallei.

Anti-Hcp1 Monoclonal Antibody Is Protective against Burkholderia pseudomallei Infection via Recognizing Amino Acids at Asp95-Leu114.

Melioidosis, a severe tropical illness caused by Burkholderia pseudomallei, poses significant treatment challenges due to limited therapeutic options and the absence of effective vaccines. The pathogen's intrinsic resistance to numerous antibiotics and propensity to induce sepsis during acute infections further complicate management strategies. Thus, exploring alternative methods for prevention and treatment is crucial. Monoclonal antibodies (mAbs) have emerged as a promising strategy for the prevention and treatment of infectious diseases. This study focused on generating three mAbs (13F1, 14G11, and 15D9) targeting hemolysin-coregulated protein 1 (Hcp1), a protein involved in the type VI secretion system cluster 1 (T6SS1) of B. pseudomallei. Notably, pretreatment with 13F1 mAb significantly reduced the intracellular survival of B. pseudomallei and inhibited the formation of macrophage-derived multinucleated giant cells (MNGCs). This protective effect was also observed in vivo. We identified a sequence of amino acids (Asp95-Leu114) within Hcp1 as the likely binding site for 13F1 mAb. In summary, our findings reveal that 13F1 mAb counteracts infection by targeting Hcp1, offering potential new targets and insights for melioidosis prevention.

Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity.

Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II) deposits as amyloid fibrils (AApoAII) and can be transmitted from one animal to another both by the feces and milk excreted by mice with amyloidosis. Thus, mouse AApoAII amyloidosis has been demonstrated to be a "transmissible disease". In this study, to further characterize the transmissibility of amyloidosis, AApoAII amyloid fibrils were injected into transgenic Apoa2(c)Tg(+/-) and normal R1.P1-Apoa2(c) mice to induce AApoAII systemic amyloidosis. Two months later, AApoAII amyloid deposits were found in the skeletal muscles of amyloid-affected mice, primarily in the blood vessels and in the interstitial tissues surrounding muscle fibers. When amyloid fibrils extracted from the skeletal muscles were subjected to Western blot analysis, apoA-II was detected. Amyloid fibril fractions isolated from the muscles not only demonstrated the structure of amyloid fibrils but could also induce amyloidosis in young mice depending on its fibril conformation. These findings present a possible pathogenesis of amyloidosis: transmission of amyloid fibril conformation through muscle, and shed new light on the etiology involved in amyloid disorders.

Structure and antioxidant activity of six mushroom-derived heterogalactans.

Heterogalactans with weight-average molecular weights ~20 kDa were purified from several species of mushroom: Hypsizygus marmoreus, Pleurotus ostreatus, Pholiota nameko, Agrocybe cylindracea, Hygrophorus lucorum and Hericium erinaceus, and structurally characterized and assessed for antioxidant activity in vitro. Methylation analysis, combined with NMR spectral analysis, indicates that these glycans have a common backbone composed of (1 â†’ 6)-linked-α-D-galactopyranosyl residues that are substituted at O-2. The (1 â†’ 6)-α-D-galactans, branched primarily with ß-D-mannopyranosyl (Manp) or α-L-fucopyranosyl (Fucp) residues, have been assigned to mannogalactans or fucogalactans, respectively, as well as to ß-D-Manp and α-L-Fucp residues attached in tandem to the main chain as fucomannogalactans. In addition, 3-O-methylated-α-D-galactopyranosyl (3-O-Me-Galp) residues within the mannogalactan chains, exhibit strong reducing power and radical scavenging activity suggesting that this sugar moiety functions as an antioxidant. Our results provide important structural information on mushroom heterogalactans and prompt further investigations into their structure-activity relationships.