bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro
Authors: Zhang Guifeng , Liu Chuang , Zhang Rentang
Published: September 2022

Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. And then BJP-2 was identified by SEC-MALLS-RI, GC-MS, methylation and NMR for the following characteristics: molecular weight of 6.42 × 104 Da, monosaccharide composition of glucuronic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), glucose (Glc), fucose (Fuc) and mannose (Man) with the percentage of 39.78, 31.93, 16.86, 6.43, 1.86, 1.28, 1.02, 0.61, and 0.23%, as well as the main chain of → 5)-α-L-Araf (1 → 4)-β-D-Gal(1 → , T-α-L-Araf (1 → 4)-β-D-Gal(1 → , and → 4)-α-L-6MeGalAp(1 → . The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent.
Novel angiotensin-converting enzyme and pancreatic lipase oligopeptide inhibitors from fermented rice bran
Authors: Hu Jingfei , Wang Huanyu , Weng Nanhai , Wei Tong , Tian Xueqing , Lu Jing , Lyu Mingsheng , Wang Shujun
Published: September 2022

This study determined the inhibitory activity of oligopeptides against angiotensin-converting enzyme (ACE) and pancreatic lipase through in vitro tests, molecular docking, and enzyme inhibition. The results showed that the IC50 of GLLGY, HWP, and VYGF for ACE inhibition was 1 mg/mL, and the IC50 of HWP for pancreatic lipase was 3.95 mg/mL. Molecular docking revealed that the binding energies between GLLGY, HWP, and VYGF and ACE were –9.0, –8.4, and –9.2 kcal/mol, respectively. The binding free energy between HWP and pancreatic lipase was –7.3 kcal/mol. GLLGY, HWP, and VYGF inhibited ACE compentitively. HWP inhibited pancreatic lipase through non-competition. in vitro simulated gastrointestinal digestion, the three oligopeptides still had inhibitory activity and low toxicity. The results revealed that the peptides GLLGY, HWP, and VYGF may be suitable candidates for further research on ACE inhibition, and HWP may be a suitable candidate for studying pancreatic lipase inhibition.
Amelioration of obesity-related metabolic disorders via supplementation of Caulerpa lentillifera in rats fed with a high-fat and high-cholesterol diet
Authors: Manoppo Jeanette Irene Christiene , Nurkolis Fahrul , Pramono Adriyan , Ardiaria Martha , Murbawani Etisa Adi , Yusuf Muhammad , Qhabibi Faqrizal Ria , Yusuf Vincentius Mario , Amar Nasim , Karim Muhammad Rico Abdul , Subali Anita Dominique , Natanael Hans , Rompies Ronald , Halim Rifrita Fransisca , Bolang Alexander Sam Leonard , Joey Gregory , Novianto Christian Agung , Permatasari Happy Kurnia
Published: September 2022

Dietary modification, including functional foods, could reduce comorbidities due to obesity. An increase in serum glucose and lipids is often seen in obesity. Furthermore, obesity is also characterized by a decrease in antioxidant capacity (i.e., decrease in superoxide dismutase/SOD) and downregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). It has been well established that PGC-1α is important to regulate mitochondrial biogenesis. Sea grapes (Caulerpa lentillifera) are known as a traditional food in many Asia-Pacific countries. Recent evidence suggests that sea grapes have many beneficial properties as functional foods and may have potential therapeutic functions. We investigated the effect of sea grapes (C. lentillifera) on serum glucose, lipids, PGC-1α, and protein levels of SOD in the liver of Rattus norvegicus, which is induced with a high-fat and high-cholesterol diet. A total of four groups were made, each containing ten male Rattus norvegicus; group A received a standard dry pellet diet as control, group B received cholesterol- and fat-enriched diets (CFED), groups C and D received CFED and 150 and 450 mg/kg body weight (BW) of sea grape extract, respectively, for 4 weeks. Serum glucose and cholesterol were assessed using a blood auto-analyzer. Serum PGC-1α was measured using ELISA. SOD levels were calculated using the superoxide dismutase assay kit by Sigma-Aldrich with blood taken from liver tissue. In this study, sea grape extracts improved total cholesterol levels better than the CFED and normal groups. The efficacy of total cholesterol improvement was similar between the two doses of sea grape extract. Furthermore, sea grape extract increased PCG-1α levels, especially with the dose of 150 mg/kg BW. Blood glucose was also lower in the groups of sea grape extract. Interestingly, the groups treated with sea grapes extract exhibited higher levels of liver SOD compared to the normal and CFED groups. To conclude, sea grapes (C. lentillifera) have promising potential for anti-hyperglycemia and anti-hypercholesterolemia, and for reducing oxidative stress, and providing various health benefits for metabolic disorders.
Association of myosteatosis with various body composition abnormalities and longer length of hospitalization in patients with decompensated cirrhosis
Authors: Wang Xiaoyu , Sun Mingyu , Li Yifan , Guo Gaoyue , Yang Wanting , Mao Lihong , Yu Zihan , Hui Yangyang , Fan Xiaofei , Cui Binxin , Jiang Kui , Sun Chao
Published: September 2022

Background

Myosteatosis is linked to dismal outcomes in the context of cirrhosis. However, the association of myosteatosis with various body composition abnormalities remains enigmatic. We aimed to clarify the determinants of myosteatosis and its relationship with other body composition profiles and length of hospitalization (LOH).

Methods

We retrospectively analyzed the data of 473 consecutive patients with cirrhosis hospitalized for decompensation. Computed tomography-based segmentation of the cross-sectional area at the third lumbar vertebra was used to evaluate body composition abnormalities. The categories of myosteatosis were built according to our previously outcome-based cutoffs for each gender.

Results

Totally, 83 patients (17.55%) were stratified as myosteatosis, of whom 85.54% had concomitant high visceral adiposity indicative of increased visceral adipose tissue index (VATI). The prevalence of sarcopenia showed no significant difference between the groups with and without myosteatosis. Multivariate analysis showed that advanced age [odds ratio (OR) = 1.097, p < 0.001], higher visceral to subcutaneous ratio of adipose tissue area (VSR; OR = 1.574, p = 0.032), and higher VATI (OR = 1.026, p < 0.001) are independently associated with myosteatosis. Correlation analyses revealed a positive relationship between intramuscular adipose tissue content (IMAC) and VATI (ρ = 0.48, p < 0.001), subcutaneous adipose tissue index (SATI) (ρ = 0.36, p < 0.001), and age (ρ = 0.36, p < 0.001). None of the skeletal muscle or adipose tissue indicators were significantly related to longer LOH.

Conclusion

Higher VSR, higher VATI, and advanced age are associated with myosteatosis among patients with cirrhosis at the decompensation phase. It is tempting to target divergent adipose tissue depots aimed at timely intervention/prevention of myosteatosis.
Composition, anti-LDL oxidation, and non-enzymatic glycosylation inhibitory activities of the flavonoids from Mesembryanthemum crystallinum
Authors: Sun Meiling , Wei Ying , Feng Xiaoguang , Fan Junfeng , Chen Xiangning
Published: September 2022

This study identified the constituents of purified flavonoid (PEF) isolated from Mesembryanthemum crystallinum and examined their inhibitory effects on low-density lipoprotein (LDL) oxidation and non-enzymatic glycosylation. More than 30 kinds of flavonoid compounds were identified in M. crystallinum, including tangeretin, nobiletin, farrerol, protocatechuic aldehyde, diosmin, and rutin. Moreover, tangeretin corresponds to approximately 51% of the total identified flavonoids. PEF had a low IC50 value for 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH·), hydroxyl radical (·OH), and superoxide anion free radical (O2-·) scavenging. They were found to effectively delay and inhibit the production of conjugated diene (CD) and thiobarbituric acid reactive substance (TBARS) during LDL oxidation. Meanwhile, scanning electron microscopy (SEM) of the LDL oxidation incubation system with PEF showed a smooth and dense surface, with no obvious cavitation phenomenon. Furthermore, PEF effectively inhibited the production of LDL glycosylation products and showed a strong inhibitory effect in the latter stage. The electrophoresis of advanced glycosylation end products (AGEs) further confirmed that PEF can effectively prevent the cross-linking between glucose and proteins, protecting LDL from glycosylation-induced damage.
Expanding the phenotypic spectrum of non-alcoholic fatty liver disease and hypertriglyceridemia
Authors: Meroni Marica , Longo Miriam , Paolini Erika , Tria Giada , Ripolone Michela , Napoli Laura , Moggio Maurizio , Fracanzani Anna Ludovica , Dongiovanni Paola
Published: September 2022

Background and aims

Hypertriglyceridemia is a common feature of metabolic syndrome (MetS), as well as of non-alcoholic fatty liver disease (NAFLD), which is considered the hepatic manifestation of MetS. Fat accumulation in hepatocytes may alter mitochondrial homeostasis predisposing to advanced liver disease. Here, we report a case of a 40-year-old woman with early aggressive NAFLD due to severe hypertriglyceridemia that ensued from a combination of genetic variants and additional metabolic risk factors.

Methods

Genetic screening was performed by using whole-exome sequencing (WES), and mitochondrial structures were evaluated by TEM.

Results

At presentation, the patient is reported to have hepatomegaly, hypertriglyceridemia, and raised transaminases. Genetic analysis revealed that the patient beard heritable alterations in genes implicated in lipid handling, among which APOB, APOE, CETP, and HSPG2, accompanied by missense mutations in genes involved in mitochondrial function, i.e., AK2, ALG6, ASPA, NDUFAF1, POLG, and TMEM70. Abdominal ultrasound (US) and transient elastography were suggestive of severe hepatic steatosis and fibrosis. A liver biopsy confirmed the diagnosis of non-alcoholic steatohepatitis (NASH)-related fibrosis. Thus, to better outline whether mutations involved in lipid remodeling and mitochondrial function may also affect organelles’ morphology, we exploited TEM. Along with multifaceted abnormalities of mitochondrial architecture that have been already observed in patients with NAFLD, astonishing ultrastructural defects, such as mitochondrial vacuolization, sub-compartmentalization, and onion-like mitochondria, were identified.

Conclusion

The anomalies reported may expand the phenotypic spectrum of mitochondrial abnormalities observed in patients with NAFLD, which may contribute to the switching toward a progressive disease.
Preterm birth and metabolic implications on later life: A narrative review focused on body composition
Authors: Casirati Amanda , Somaschini Alberto , Perrone Michela , Vandoni Giulia , Sebastiani Federica , Montagna Elisabetta , Somaschini Marco , Caccialanza Riccardo
Published: September 2022

Preterm newborn infants are characterized by low body weight and lower fat mass at birth compared with full-term newborn neonates. Conversely, at term corrected age, body fat mass is more represented in preterm newborn infants, causing a predisposition to developing metabolic syndrome and cardiovascular diseases in later life with a different risk profile in men as compared with women. Postnatal growth is a complex change in anthropometric parameters and body composition. Both quantity and quality of growth are regulated by several factors such as fetal programming, early nutrition, and gut microbiota. Weight gain alone is not an optimal indicator of nutritional status as it does not accurately describe weight quality. The analysis of body composition represents a potentially useful tool to predict later metabolic and cardiovascular risk as it detects the quality of growth by differentiating between fat and lean mass. Longitudinal follow-up of preterm newborn infants could take advantage of body composition analysis in order to identify high-risk patients who apply early preventive strategies. This narrative review aimed to examine the state-of-the-art body composition among born preterm children, with a focus on those in the pre-school age group.
The gut microbiome and Alopecia areata: Implications for early diagnostic biomarkers and novel therapies
Authors: Kang Yongbo , Cai Yue , Zhao Yanqin , Yang Ying
Published: September 2022

Alopecia areata (AA) accounts for the autoimmune disorder mediated by T cells, whose prognostic outcome cannot be predicted and curative treatment is unavailable at present. The AA pathogenic mechanism remains largely unclear, even though follicular attack has been suggested to result from that attack of immune privilege-losing hair follicles driven by immunity. Recently, gut microbiota is suggested to have an important effect on immunoregulation under autoimmune situations like AA. Fecal microbial transplantation (FMT) may be used to treat AA. Nonetheless, related research remains at the initial stage. To promote the rapid progress of relevant research, the present work aimed to shed more lights on gut microbiota's effect on AA, early diagnostic biomarker and FMT therapeutics.
Ponciri Fructus Immaturus ethanol extract attenuates septic shock through inhibition of the STAT1 signaling pathway
Authors: Hwang Yo Sep , Jang Jun-Pil , Park Seong-Hoon , Kim Aeyung , Jang Jae-Hyuk , Yoon Hyang Ran , Yoon Suk Ran , Park Jun Hong , Cho Hee Jun , Lee Hee Gu
Published: September 2022

Sepsis is a systemic inflammatory disease to infections and results in tissue damage and multiple organ failure. Ponciri Fructus Immaturus (PFI) is widely used in traditional medicine for allergic inflammation and gastrointestinal disorders. However, the effect of PFI on sepsis is still unknown. This study investigated the anti-inflammatory and antiseptic effects of PFI ethanol extract (PFIE) in LPS-stimulated J774 macrophages and mice with CLP- or LPS-induced sepsis, respectively. PFIE attenuates the LPS-induced production of the proinflammatory mediator NO by inhibiting the expression of iNOS in J774 cells. Real-time RT-PCR data and ELISA showed that the mRNA and protein levels of TNF-α, IL-1β, and IL-6 increased in LPS-stimulated J774 cells. However, this induction was significantly suppressed in PFIE pre-treated J774 cells. We also found that PFIE administration increased the survival rate of mice with LPS- and CLP-induced sepsis. Decreased serum levels of AST, ALT, and CK were observed after administration of PFIE, which was associated with reduced production of proinflammatory factors, such as NO, TNF-α, IL-1β, and IL-6. Moreover, PFIE suppressed the phosphorylation and nuclear translocation of STAT1 in LPS-stimulated J774 cells, suggesting that PFIE can inhibit LPS- and CLP-induced septic shock by suppressing the STAT1 activation. These findings provide the potential therapeutic relevance of PFIE in treating acute inflammatory disease.
Polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles: Characterization, immunological effect and mechanism
Authors: Bo Ruonan , Liu Xiaopan , Wang Jing , Wei Simin , Wu Xinyue , Tao Ya , Xu Shuya , Liu Mingjiang , Li Jingui , Pang Huan
Published: September 2022

Atractylodes macrocephala Koidz (A. macrocephala) has been used both as a traditional medicine and functional food for hundreds of years in Asia. And it has a variety of biological activities, such as enhancing the ability of immunity and modulating effect on gastrointestinal motility. In this study, a water-soluble polysaccharide with molecular weight of 2.743 × 103 Da was isolated from the root of A. macrocephala. Polysaccharide from A. macrocephala (AMP) consisted of arabinose, galactose, glucose, xylose, mannose, ribose, galactose uronic acid, glucose uronic acid, with a percentage ratio of 21.86, 12.28, 34.19, 0.43, 0.92, 0.85, 28.79, and 0.67%, respectively. Zinc plays an important role in immune system. Therefore, we supposed that AMP binding with zinc oxide (ZnO) nanoparticles (AMP-ZnONPs) might be an effective immunostimulator. AMP-ZnONPs was prepared by Borch reduction, and its structural features were characterized by Scanning Electron Microscope (SEM), Transmission electron microscope (TEM), TEM-energy dispersive spectroscopy mapping (TEM-EDS mapping), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), X-ray diffraction (XRD), particle size and zeta-potential distribution analysis. Then, its immunostimulatory activity and the underlying mechanism were evaluated using RAW264.7 cells. The results showed that AMP-ZnONPs remarkably promoted cell proliferation, enhanced phagocytosis, the release of nitric oxide (NO), cytokines (IL-6 and IL-1β) and the expression of co-stimulatory molecules (CD80, CD86 and MHCII). Moreover, AMP-ZnONPs could promote the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), TNF receptor associated factor 6 (TRAF6), phospho-IκBα (P-IκBα) and phospho-p65 (P-p65), and TLR4 inhibitor (TAK242) inhibited the expression of these proteins induced by AMP-ZnONPs. Therefore, AMP-ZnONPs activated macrophages by TLR4/MyD88/NF-κB signaling pathway, indicating that AMP-ZnONPs could act as a potential immunostimulator in medicine and functional food.
Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer
Authors: Rittberg Rebekah , Leung Bonnie , Al-Hashami Zamzam , Ho Cheryl
Published: September 2022

Introduction

Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.

Methods

A retrospective cohort analysis was conducted of referred ES SCLC between 2015 and 2017 in British Columbia, Canada. Patient demographics, staging, treatment, and survival data were collected through the Cancer Registry. Retrospective chart review was completed to extract past medical history and missing variables. CASPIAN/IMPower133 excluded patients with autoimmune diseases, active infection, and performance status (PS) ≥2.

Results

Between 2015 and 2017, 349 patients were diagnosed with ES SCLC. In patients who received platinum-doublet chemotherapy (n=227), 15 had medical contraindication to ICI: inflammatory bowel disease (n=4), rheumatoid arthritis (n=4), idiopathic pulmonary fibrosis (n=3), lupus (n=1), Sjogren’s (n=1), Takayasu arteritis (n=1), and active tuberculosis (n=1). ECOG PS was 0–1 in 96 (45%), PS was 2 in 61 (29%), and ≥3 in 51 (10%). Prior to cycle 1, 82 (36%) patients were eligible for ICI in addition to platinum doublet, 23% of the entire ES population. After cycles 1 and 2, additional 15 (7%) and 8 (4%) patients became PS 0–1, respectively. mOS for ES SCLC who received first-line platinum doublet, non-platinum chemotherapy, and best supportive care was 8.4 1.9 and 1.5 months (p<0.001).

Discussion

By CASPIAN/IMpower133 trial eligibility, only 36% of our real-world platinum-treated patients would have been eligible for the addition of ICI, which is 23% of the entire ES population in one Canadian province. After one or two cycles of chemotherapy, an additional 11% of patients showed PS improvement to 0–1. While the results of CASPIAN/IMpower133 are practice-changing, the majority of the patients will not meet clinical trial eligibility and clinical trials including patients with poor PS are necessary.
Radiosensitization effect by HDAC inhibition improves NKG2D-dependent natural killer cytotoxicity in hepatocellular carcinoma
Authors: Liu Yu-Fan , Chiang Yun , Hsu Feng-Ming , Tsai Chiao-Ling , Cheng Jason Chia-Hsien
Published: September 2022

Background

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Radiotherapy (RT) controls HCC unsatisfactorily and temporarily. Histone deacetylase inhibitor (HDACi) is a heterogeneous group of epigenetic therapeutics with promising anticancer effects and synergism in combination with RT. HDACi modulates natural killer (NK) cell ligand expression on tumor cells, and leads to immune evasion of cancer cells. Expressions of NK group 2D (NKG2D) ligands on cancer cells determine the cytotoxic effect by interacting with NKG2D receptor on NK cells. However, the role of NKG2D signaling in HCC upon combined RT and HDACi remains unclear.

Method

In vitro co-culture system with NK cells was tested for human and murine HCC cell lines. Pan-HDACi (panobinostat) and specific HDAC4 knockdown (HDAC4-KD) were used for HDAC inhibition. Clonogenic assay and flow cytometry examined HCC cell survival and NKG2D ligand expression, respectively. Syngeneic mouse model was used to validate the radiosensitizing effect in vivo.

Results

Combined RT and HDACi/HDAC4-KD significantly enhanced NK cell-related cytotoxicity and increased NKG2D ligands, MICA/MICB expressions in human and RAE-1/H60 expressions in murine HCC cells. Delayed tumor growth in vivo by the combinational treatment of RT and HDACi/HDAC4-KD was shown with the associated NKG2D ligand expressions. However, NKG2D receptor did not significantly change among tumors.

Conclusion

Radiosensitizing effect with combined RT and HDAC inhibition increased the expression of NKG2D ligands in HCC cells and enhanced their susceptibility to NK cell-mediated cytotoxicity. These findings imply the potential use of combined RT/HDACi and NK cell-directed immunotherapy.
A computed tomography-based preoperative risk scoring system to distinguish lymphoepithelioma-like gastric carcinoma from non-lymphoepithelioma-like gastric carcinoma
Authors: Li Liming , Huang Wenpeng , Hou Ping , Li Weiwei , Feng Menyun , Liu Yiyang , Gao Jianbo
Published: September 2022

Purpose

The aim of this study was to develop a preoperative risk scoring model for distinguishing lymphoepithelioma-like gastric carcinoma (LELGC) from non-LELGC based on contrast-enhanced computed tomography (CT) images.

Methods

Clinicopathological features and CT findings of patients with LELGC and non-LELGC in our hospital from January 2016 to July 2022 were retrospectively analyzed and compared. A preoperative risk stratification model and a risk scoring system were developed using logistic regression.

Results

Twenty patients with LELGC and 40 patients with non-LELGC were included in the training cohort. Significant differences were observed in Epstein–Barr virus (EBV) infection and vascular invasion between the two groups (p < 0.05). Significant differences were observed in the distribution of location, enhancement pattern, homogeneous enhancement, CT-defined lymph node status, and attenuations in the non-contrast, arterial, and venous phases (all p < 0.05). Enhancement pattern, CT-defined lymph node status, and attenuation in venous phase were independent predictors of LELGC. The optimal cutoff score of distinguishing LELGC from non-LELGC was 3.5. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the training cohort were 0.904, 87.5%, 80.0%, and 85.0%, respectively. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the validation cohort were 0.705 (95% CI 0.434–0.957), 75.0%, 63.6%, and 66.7%, respectively.

Conclusion

A preoperative risk identification model based on CT imaging data could be helpful for distinguishing LELGC from non-LELGC.
Relative T2-FLAIR signal intensity surrounding residual cavity is associated with survival prognosis in patients with lower-grade gliomas
Authors: Yuan Tao , Gao Zhen , Wang Fei , Ren Jia-Liang , Wang Tianda , Zhong Hongbo , Gao Guodong , Quan Guanmin
Published: September 2022

Aims

To investigate whether the relative signal intensity surrounding the residual cavity on T2-fluid-attenuated inversion recovery (rFLAIR) can improve the survival prediction of lower-grade glioma (LGG) patients.

Methods

Clinical and pathological data and the follow-up MR imaging of 144 patients with LGG were analyzed. We calculated rFLAIR with Image J software. Logistic analysis was used to explore the significant impact factors on progression-free survival (PFS) and overall survival (OS). Several models were set up to predict the survival prognosis of LGG.

Results

A higher rFLAIR [1.81 (0.83)] [median (IQR)] of non-enhancing regions surrounding the residual cavity was detected in the progressed group (n=77) than that [1.55 (0.33)] [median (IQR)] of the not-progressed group (n = 67) (P<0.001). Multivariate analysis showed that lower KPS (≤75), and higher rFLAIR (>1.622) were independent predictors for poor PFS (P<0.05), whereas lower KPS (≤75) and thick-linear and nodular enhancement were the independent predictors for poor OS (P<0.05). The cutoff rFLAIR value of 1.622 could be used to predict poor PFS (HR = 0.31, 95%CI 0.20–0.48) (P<0.001) and OS (HR = 0.27, 95%CI 0.14–0.51) (P=0.002). Both the areas under the ROC curve (AUCs) for predicting poor PFS (AUC, 0.771) and OS (AUC, 0.831) with a combined model that contained rFLAIR were higher than those of any other models.

Conclusion

Higher rFALIR (>1.622) in non-enhancing regions surrounding the residual cavity can be used as a biomarker of the poor survival of LGG. rFLAIR is helpful to improve the survival prediction of posttreatment LGG patients.
Case report: A Saprochaete clavata (Magnusiomyces clavatus) severe infection effectively treated with granulocyte transfusion in a young patient with myeloid sarcoma
Authors: Pasqualone Gianmario , Buzzatti Elisa , Palmieri Raffaele , Savi Arianna , Pascale Maria Rosaria , Borsellino Beatrice , Guarnera Luca , Buccisano Francesco , Voso Maria Teresa , Maurillo Luca , Sconocchia Giuseppe , Venditti Adriano , Del Principe Maria Ilaria
Published: September 2022

Myeloid sarcoma is a hematologic malignancy consisting of extramedullary tissue involvement by myeloid blasts, usually considered as acute myeloid leukemia and treated accordingly. The disease itself, together with chemotherapy and disease-associated factors, may have an impact in increasing the risk of developing severe and frequently life-threatening infections. Herein, we describe the case of a patient with a right breast skin lesion, histologically diagnosed myeloid sarcoma, who developed a severe disseminated fungal infection by Saprochaete clavata (Magnusiomyces clavatus), during the first consolidation course of chemotherapy. Despite maximum antifungal therapy, the infection progressed and the fungus continued to be isolated until granulocyte transfusion therapy was initiated. Our experience suggests that patients with profound and long-lasting neutropenia could benefit from granulocyte transfusions as additional therapy in severe fungal infections resistant to broad-spectrum antimicrobial therapy.
Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma
Authors: Cox Amanda , Nierenberg Daniel , Camargo Oscar , Lee Eunkyung , Khaled Amr S. , Mazar Joseph , Boohaker Rebecca J. , Westmoreland Tamarah J. , Khaled Annette R.
Published: September 2022

Chaperonin containing TCP1 (CCT/TRiC) is a multi-subunit protein folding complex that enables the cancer phenotype to emerge from the mutational landscape that drives oncogenesis. We and others linked increased expression of CCT subunits to advanced tumor stage and invasiveness that inversely correlates with cancer patient outcomes. In this study, we examined the expression of the second CCT subunit, CCT2, using genomic databases of adult and pediatric tumors and normal tissues, and found that it was highly expressed in pediatric cancers, showing a significant difference compared to normal tissues. Histologic staining confirmed that CCT subunits are highly expressed in tumor tissues, which was exemplified in neuroblastoma. Using two neuroblastoma cells, MYCN-amplified, IMR-32 cells, and non-amplified, SK-N-AS cells, we assessed baseline levels for CCT subunits and found expressions comparable to the highly invasive triple-negative breast cancer (TNBC) cell line, MDA-MB-231. Exogenous expression of CCT2 in both SK-N-AS and IMR-32 cells resulted in morphological changes, such as larger cell size and increased adherence, with significant increases in the CCT substrates, actin, and tubulin, as well as increased migration. Depletion of CCT2 reversed these effects and reduced cell viability. We evaluated CCT as a therapeutic target in IMR-32 cells by testing a novel peptide CCT inhibitor, CT20p. Treatment with CT20p induced cell death in these neuroblastoma cells. The use of CCT2 as a biological indicator for detection of neuroblastoma cells shed in blood was examined by spiking IMR-32 cells into human blood and using an anti-CCT2 antibody for the identification of spiked cancer cells with the CellSearch system. Results showed that using CCT2 for the detection of neuroblastoma cells in blood was more effective than the conventional approach of using epithelial markers like cytokeratins. CCT2 plays an essential role in promoting the invasive capacity of neuroblastoma cells and thus offers the potential to act as a molecular target in the development of novel therapeutics and diagnostics for pediatric cancers.
Cardiovascular disease related death among patients with esophagus cancer: A population-based competing risk analysis
Authors: Xia Yang , Lin Min , Huang Jin , Fan Li
Published: September 2022

The proportion of non-cancer death in patients with esophagus cancer (EC) still increasing, especially cardiovascular disease (CVD) related death. The aim of this study was assess non-cancer causes of death and identified independent risk factors of CVD related death in EC patients. Patients diagnosed with EC were extracted from the Surveillance, Epidemiology, and End Result database (SEER) database for analysis. Standardized mortality rates (SMRs) for non-EC deaths were calculated, the risk of death were assessed and compared with US general population. Multivariate competitive risk analysis were performed to select independent risk factors for death from CVD in EC patients. A total of 43739 EC patients were enrolled and 35139 died during follow-up, of which 4248 died from non-cancer cause of death. The risk of non-cancer death in EC patients was 2.27-fold higher than in the general population (SMR=2.27; 95% CI, 2.20-2.34). CVD were the most important cause of non-cancer death in EC patients, accounting for 43.4% of non-cancer of deaths. Compare with the general population, EC patients have higher risk of death from disease of heart (SMR, 2.24; 95% CI, 2.13-2.35), pneumonia and influenza (SMR, 2.92; 95% CI, 2.50-3.39), septicemia (SMR, 5.01; 95% CI, 4.30-5.79), along with other causes. Patients with advanced age and patients who received radiotherapy has higher risk of death caused by CVD, patients with female sex, poor differentiated and undifferentiated, regional and distant stage, married, diagnosed between 2010-2016 has lower risk of CVD related death, compared with patients without any treatment measures, patients received chemotherapy alone has lower risk of death from CVD. Non-cancer cause of death has become an important cause of death in EC patients. Improving public awareness of the major risk factors for non-cancer death is beneficial to the prevention and treatment of malignant tumors.
Prediction of lymph node metastasis in patients with breast invasive micropapillary carcinoma based on machine learning and SHapley Additive exPlanations framework
Authors: Jiang Cong , Xiu Yuting , Qiao Kun , Yu Xiao , Zhang Shiyuan , Huang Yuanxi
Published: September 2022

Background and purpose: Machine learning (ML) is applied for outcome prediction and treatment support. This study aims to develop different ML models to predict risk of axillary lymph node metastasis (LNM) in breast invasive micropapillary carcinoma (IMPC) and to explore the risk factors of LNM.

Methods

From the Surveillance, Epidemiology, and End Results (SEER) database and the records of our hospital, a total of 1547 patients diagnosed with breast IMPC were incorporated in this study. The ML model is built and the external validation is carried out. SHapley Additive exPlanations (SHAP) framework was applied to explain the optimal model; multivariable analysis was performed with logistic regression (LR); and nomograms were constructed according to the results of LR analysis.

Results

Age and tumor size were correlated with LNM in both cohorts. The luminal subtype is the most common in patients, with the tumor size <=20mm. Compared to other models, Xgboost was the best ML model with the biggest AUC of 0.813 (95% CI: 0.7994 - 0.8262) and the smallest Brier score of 0.186 (95% CI: 0.799-0.826). SHAP plots demonstrated that tumor size was the most vital risk factor for LNM. In both training and test sets, Xgboost had better AUC (0.761 vs 0.745; 0.813 vs 0.775; respectively), and it also achieved a smaller Brier score (0.202 vs 0.204; 0.186 vs 0.191; 0.220 vs 0.221; respectively) than the nomogram model based on LR in those three different sets. After adjusting for five most influential variables (tumor size, age, ER, HER-2, and PR), prediction score based on the Xgboost model was still correlated with LNM (adjusted OR:2.73, 95% CI: 1.30-5.71, P=0.008).

Conclusions

The Xgboost model outperforms the traditional LR-based nomogram model in predicting the LNM of IMPC patients. Combined with SHAP, it can more intuitively reflect the influence of different variables on the LNM. The tumor size was the most important risk factor of LNM for breast IMPC patients. The prediction score obtained by the Xgboost model could be a good indicator for LNM.
Pharmacological effects and therapeutic potential of natural compounds in neuropsychiatric disorders: An update
Authors: Asgharian Parina , Quispe Cristina , Herrera-Bravo Jesús , Sabernavaei Mahsa , Hosseini Kamran , Forouhandeh Haleh , Ebrahimi Tahereh , Sharafi-Badr Paria , Tarhriz Vahideh , Soofiyani Saiedeh Razi , Helon Paweł , Rajkovic Jovana , Durna Daştan Sevgi , Docea Anca Oana , Sharifi-Rad Javad , Calina Daniela , Koch Wojciech , Cho William C.
Published: September 2022

Neuropsychiatric diseases are a group of disorders that cause significant morbidity and disability. The symptoms of psychiatric disorders include anxiety, depression, eating disorders, autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder, and conduct disorder. Various medicinal plants are frequently used as therapeutics in traditional medicine in different parts of the world. Nowadays, using medicinal plants as an alternative medication has been considered due to their biological safety. Despite the wide range of medications, many patients are unable to tolerate the side effects and eventually lose their response. By considering the therapeutic advantages of medicinal plants in the case of side effects, patients may prefer to use them instead of chemical drugs. Today, the use of medicinal plants in traditional medicine is diverse and increasing, and these plants are a precious heritage for humanity. Investigation about traditional medicine continues, and several studies have indicated the basic pharmacology and clinical efficacy of herbal medicine. In this article, we discuss five of the most important and common psychiatric illnesses investigated in various studies along with conventional therapies and their pharmacological therapies. For this comprehensive review, data were obtained from electronic databases such as MedLine/PubMed, Science Direct, Web of Science, EMBASE, DynaMed Plus, ScienceDirect, and TRIP database. Preclinical pharmacology studies have confirmed that some bioactive compounds may have beneficial therapeutic effects in some common psychiatric disorders. The mechanisms of action of the analyzed biocompounds are presented in detail. The bioactive compounds analyzed in this review are promising phytochemicals for adjuvant and complementary drug candidates in the pharmacotherapy of neuropsychiatric diseases. Although comparative studies have been carefully reviewed in the preclinical pharmacology field, no clinical studies have been found to confirm the efficacy of herbal medicines compared to FDA-approved medicines for the treatment of mental disorders. Therefore, future clinical studies are needed to accelerate the potential use of natural compounds in the management of these diseases.
Pharmacological effects of higenamine based on signalling pathways and mechanism of action
Authors: Chen De-ta , Rao Wu , Shen Xue , Chen Lin , Wan Zi-jian , Sheng Xiao-ping , Fan Tian-you
Published: September 2022

Higenamine (HG) is a chemical compound found in various plants, such as aconite. Recent pharmacological studies have demonstrated its effectiveness in the management of many diseases. Several mechanisms of action of HG have been proposed; however, they have not yet been classified. This review summarises the signalling pathways and pharmacological targets of HG, focusing on its potential as a naturally extracted drug. Articles related to the pharmacological effects, signalling pathways and pharmacological targets of HG were selected by searching the keyword “Higenamine” in the PubMed, Web of Science and Google Scholar databases without limiting the search by publication years. HG possesses anti-oxidant, anti-apoptotic, anti-inflammatory, electrophysiology regulatory, anti-fibrotic and lipid-lowering activities. It is a structural analogue of catecholamines and possesses characteristics similar to those of adrenergic receptor ligands. It can modulate multiple targets, including anti-inflammation- and anti-apoptosis-related targets and some transcription factors, which directly or indirectly influence the disease course. Other naturally occurring compounds, such as cucurbitacin B (Cu B) and 6-gingerol (6-GR), can be combined with HG to enhance its anti-apoptotic activity. Although significant research progress has been made, follow-up pharmacological studies are required to determine the exact mechanism of action, new signalling pathways and targets of HG and the effects of using it in combination with other drugs.
Sepsis-induced AKI: From pathogenesis to therapeutic approaches
Authors: He Fang-Fang , Wang Yu-Mei , Chen Yi-Yuan , Huang Wei , Li Zi-Qi , Zhang Chun
Published: September 2022

Sepsis is a heterogenous and highly complex clinical syndrome, which is caused by infectious or noninfectious factors. Acute kidney injury (AKI) is one of the most common and severe complication of sepsis, and it is associated with high mortality and poor outcomes. Recent evidence has identified that autophagy participates in the pathophysiology of sepsis-associated AKI. Despite the use of antibiotics, the mortality rate is still at an extremely high level in patients with sepsis. Besides traditional treatments, many natural products, including phytochemicals and their derivatives, are proved to exert protective effects through multiple mechanisms, such as regulation of autophagy, inhibition of inflammation, fibrosis, and apoptosis, etc. Accumulating evidence has also shown that many pharmacological inhibitors might have potential therapeutic effects in sepsis-induced AKI. Hence, understanding the pathophysiology of sepsis-induced AKI may help to develop novel therapeutics to attenuate the complications of sepsis and lower the mortality rate. This review updates the recent progress of underlying pathophysiological mechanisms of sepsis-associated AKI, focuses specifically on autophagy, and summarizes the potential therapeutic effects of phytochemicals and pharmacological inhibitors.
Typing characteristics of metabolism-related genes in osteoporosis
Authors: Guo Jiandong , Huang Qinghua , Zhou Yundong , Xu Yining , Zong Chenyu , Shen Panyang , Ma Yan , Zhang Jinxi , Cui Yongfeng , Yu Liuqian , Gao Jiawei , Liu Gang , Huang Kangmao , Xu Wenbin
Published: September 2022

Objective: Osteoporosis is a common musculoskeletal disease. Fractures caused by osteoporosis place a huge burden on global healthcare. At present, the mechanism of metabolic-related etiological heterogeneity of osteoporosis has not been explored, and no research has been conducted to analyze the metabolic-related phenotype of osteoporosis. This study aimed to identify different types of osteoporosis metabolic correlates associated with underlying pathogenesis by machine learning.

Methods: In this study, the gene expression profiles GSE56814 and GSE56815 of osteoporosis patients were downloaded from the GEO database, and unsupervised clustering analysis was used to identify osteoporosis metabolic gene subtypes and machine learning to screen osteoporosis metabolism-related characteristic genes. Meanwhile, multi-omics enrichment was performed using the online Proteomaps tool, and the results were validated using external datasets GSE35959 and GSE7429. Finally, the immune and stromal cell types of the signature genes were inferred by the xCell method.

Results: Based on unsupervised cluster analysis, osteoporosis metabolic genotyping can be divided into three distinct subtypes: lipid and steroid metabolism subtypes, glycolysis-related subtypes, and polysaccharide subtypes. In addition, machine learning SVM identified 10 potentially metabolically related genes, GPR31, GATM, DDB2, ARMCX1, RPS6, BTBD3, ADAMTSL4, COQ6, B3GNT2, and CD9.

Conclusion: Based on the clustering analysis of gene expression in patients with osteoporosis and machine learning, we identified different metabolism-related subtypes and characteristic genes of osteoporosis, which will help to provide new ideas for the metabolism-related pathogenesis of osteoporosis and provide a new direction for follow-up research.
Ghost crystallography
Authors: Zhang Minghui , Wei Huazhe , Liu Xianlong , Hoenders Bernhard J. , Guo Lina , Cai Yangjian
Published: September 2022

In [Opt. Lett. 38, 4023-4025 (2013)] the author predicted that the low coherent X-ray is hard to provide a high-resolution diffraction pattern from an object with a spatially periodic structure. This would severely restrict X-ray crystallography and its similar techniques. In this letter, we indicate that the Ghost diffraction technic takes advantage of the low coherence and may thus break through the bottleneck. Analytical formulae for calculating ghost diffraction patterns diffracted by the periodic structured media under any coherent state are derived.
Modulation of hepatic amyloid precursor protein and lipoprotein receptor-related protein 1 by chronic alcohol intake: Potential link between liver steatosis and amyloid-β
Authors: Garcia Jerome , Chang Rudy , Steinberg Ross A. , Arce Aldo , Yang Joshua , Van Der Eb Peter , Abdullah Tamara , Chandrashekar Devaraj V. , Eck Sydney M. , Meza Pablo , Liu Zhang-Xu , Cadenas Enrique , Cribbs David H. , Kaplowitz Neil , Sumbria Rachita K. , Han Derick
Published: September 2022

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting a potential link between liver injury and microglial loss in the brain. Intragastric alcohol feeding significantly affected two hepatic proteins important in amyloid-beta (Aβ) processing by the liver: 1) alcohol feeding downregulated lipoprotein receptor-related protein 1 (LRP1, ∼46%), the major receptor in the liver that removes Aβ from blood and peripheral organs, and 2) alcohol significantly upregulated APP (∼2-fold), a potentially important source of Aβ in the periphery and brain. The decrease in hepatic LRP1 and increase in hepatic APP likely switches the liver from being a remover or low producer of Aβ to an important source of Aβ in the periphery, which can impact the brain. The downregulation of LRP1 and upregulation of APP in the liver was observed in the first week of intragastric alcohol feeding, and also occurred in other alcohol feeding models (NIAAA binge alcohol model and intragastric alcohol feeding to rats). Modulation of hepatic LRP1 and APP does not seem alcohol-specific, as ob/ob mice with significant steatosis also had declines in LRP1 and increases in APP expression in the liver. These findings suggest that liver steatosis rather than alcohol-induced liver injury is likely responsible for regulation of hepatic LRP1 and APP. Both obesity and alcohol intake have been linked to AD and our data suggests that liver steatosis associated with these two conditions modulates hepatic LRP1 and APP to disrupt Aβ processing by the liver to promote AD.
Inhibition of Ca2+ entry by capsazepine analog CIDD-99 prevents oral squamous carcinoma cell proliferation
Authors: Sun Yuyang , Zboril Emily K. , De La Chapa Jorge J. , Chai Xiufang , Da Conceicao Viviane Nascimento , Valdez Matthew C. , McHardy Stanton F. , Gonzales Cara B. , Singh Brij B.
Published: September 2022

Oral cancer patients have a poor prognosis, with approximately 66% of patients surviving 5-years after diagnosis. Treatments for oral cancer are limited and have many adverse side effects; thus, further studies are needed to develop drugs that are more efficacious. To achieve this objective, we developed CIDD-99, which produces cytotoxic effects in multiple oral squamous cell carcinoma (OSCC) cell lines. While we demonstrated that CIDD-99 induces ER stress and apoptosis in OSCC, the mechanism was unclear. Investigation of the Bcl-family of proteins showed that OSCC cells treated with CIDD-99 undergo downregulation of Bcl-XL and Bcl-2 anti-apoptotic proteins and upregulation of Bax (pro-apoptotic). Importantly, OSCC cells treated with CIDD-99 displayed decreased calcium signaling in a dose and time-dependent manner, suggesting that blockage of calcium signaling is the key mechanism that induces cell death in OSCC. Indeed, CIDD-99 anti-proliferative effects were reversed by the addition of exogenous calcium. Moreover, electrophysiological properties further established that calcium entry was via the non-selective TRPC1 channel and prolonged CIDD-99 incubation inhibited STIM1 expression. CIDD-99 inhibition of calcium signaling also led to ER stress and inhibited mitochondrial complexes II and V in vitro. Taken together, these findings suggest that inhibition of TRPC mediates induction of ER stress and mitochondrial dysfunction as a part of the cellular response to CIDD-99 in OSCC.