bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the potential of Glycyrrhiza glabra as a bioavailability enhancer of Vitamin B12
Authors: Sharma Priyanka , Pathak Priyanka , Tyagi Vidushi , Khan Feroz , Shanker Karuna , Darokar Mahendra Pandurang , Pal Anirban
Published: October 2022

Vitamin B12 deficiency is prevalent among individuals globally. Inadequate consumption of B12 rich diet and low bioavailability (due to diet based/physiological factors) are linked to the deficiency of Vitamin B12 inside the body. Bioavailability enhancers augment the bioavailability of an ingested substance (drug/nutrient) thus increasing their concentration inside the body and maximizing their therapeutic benefits. In traditional medicine, Licorice (Glycyrrhiza glabra) finds utility in the treatment of various health conditions. Thus, the present study aimed to examine the potential of ethanolic extract obtained from G. glabra roots to enhance the bioavailability of Vitamin B12. The effect of ethanolic extract of G. glabra (GgEtOH) on intestinal absorption enhancement of B12 was assessed in vitro on Caco-2 and ex-vivo everted gut sac models. The influence of extract on the pharmacokinetics of Vitamin B12 was determined in vivo in Swiss albino mice. GgEtOH significantly enhanced the permeation (Papp) of B12 by 2-5 fold in vitro (25, 50, and 100 μg/ml concentrations) and ex-vivo (250 and 500 μg/ml concentrations). The pharmacokinetic parameters of B12 such as Cmax, AUC, Tmax, etc. were also significantly elevated in vivo upon oral administration of B12 (1 mg/kg dose) in combination with GgEtOH (100 and 1,000 mg/kg dose). These preliminary findings indicate that the ethanolic extract of G. glabra is capable of enhancing the bioavailability of Vitamin B12. To the best of our knowledge, this is the first report to demonstrate herbal extract-mediated enhancement of Vitamin B12 bioavailability through in vitro, ex vivo, and in vivo assays.
Why context matters when changing the diet: A narrative review of placebo, nocebo, and psychosocial context effects and implications for outcome research and nutrition counselling
Authors: Neumann Melanie , Wirtz Markus Antonius , Lutz Gabriele , Ernesti Alina , Edelhäuser Friedrich
Published: October 2022

Placebo (PE) and nocebo effects (NE) have been subjects of systematic research in medicine and psychotherapy for many decades to distinguish between the (specific) pharmacological effect of medication and the (unspecific) effect of the context. Despite this significant research, the awareness, operationalisation, and reflection of the multiplicity of PE, NE, and psychosocial context effects (PSCE) is currently limited when researching outcomes of diet changes in studies without randomisation and placebo control. This neglection is critical as it could systematically influence outcomes by moderating and mediating them and thus reducing the validity and evidence base of these studies. Therefore, we performed a (non-systematic) narrative review (NR) on the following objectives: (1) present a concise overview about the relevance of PE, NE, and PSCE in medicine and nutrition research; (2) review the current state of research on reflecting context effects when studying diet changes; (3) provide useful theoretical foundations via consideration and integration of micro- and macro context effects; (4) operationalise as hypotheses the potential PE, NE, and PSCE which are specific for researching diet changes; and (5) derive their impact for future research as well as for nutrition counselling. The electronic search in this NR for objective (2) identified N = 5 publications and for objective (4) we found N = 61 articles retrieved in the first round of search, additional references were identified by a manual and snowball search among the cited references resulting finally in N = 37. This NR offers a synoptical basis to foster awareness and operationalisation of a variety of PE, NE, and PSCE. Interdisciplinary research teams should monitor these factors using, e.g., qualitative, mixed-method studies, process evaluation, item bank approaches, moderator and mediator analysis that might reveal substantially new insights, and outcomes of relevance to science and nutrition counselling. Nevertheless, the present NR has several limitations, especially as it is non-systematic, because it is a very heterogeneous field of research, in which the topic we are investigating is usually regarded as marginal and subordinate. Therefore, future research should conduct systematic reviews and particularly theory-based primary studies (experimental research) on hypotheses of PE, NE, and PSCE in outcome research in diet changes.
May phytophenolics alleviate aflatoxins-induced health challenges? A holistic insight on current landscape and future prospects
Authors: Rasouli Hassan , Nayeri Fatemeh Dehghan , Khodarahmi Reza
Published: October 2022

The future GCC-connected environmental risk factors expedited the progression of nCDs. Indeed, the emergence of AFs is becoming a global food security concern. AFs are lethal carcinogenic mycotoxins, causing damage to the liver, kidney, and gastrointestinal organs. Long-term exposure to AFs leads to liver cancer. Almost a variety of food commodities, crops, spices, herbaceous materials, nuts, and processed foods can be contaminated with AFs. In this regard, the primary sections of this review aim to cover influencing factors in the occurrence of AFs, the role of AFs in progression of nCDs, links between GCC/nCDs and exposure to AFs, frequency of AFs-based academic investigations, and world distribution of AFs. Next, the current trends in the application of PPs to alleviate AFs toxicity are discussed. Nearly, more than 20,000 published records indexed in scientific databases have been screened to find recent trends on AFs and application of PPs in AFs therapy. Accordingly, shifts in world climate, improper infrastructures for production/storage of food commodities, inconsistency of global polices on AFs permissible concentration in food/feed, and lack of the public awareness are accounting for a considerable proportion of AFs damages. AFs exhibited their toxic effects by triggering the progression of inflammation and oxidative/nitrosative stress, in turn, leading to the onset of nCDs. PPs could decrease AFs-associated oxidative stress, genotoxic, mutagenic, and carcinogenic effects by improving cellular antioxidant balance, regulation of signaling pathways, alleviating inflammatory responses, and modification of gene expression profile in a dose/time-reliant fashion. The administration of PPs alone displayed lower biological properties compared to co-treatment of these metabolites with AFs. This issue might highlight the therapeutic application of PPs than their preventative content. Flavonoids such as quercetin and oxidized tea phenolics, curcumin and resveratrol were the most studied anti-AFs PPs. Our literature review clearly disclosed that considering PPs in antioxidant therapies to alleviate complications of AFs requires improvement in their bioavailability, pharmacokinetics, tissue clearance, and off-target mode of action. Due to the emergencies in the elimination of AFs in food/feedstuffs, further large-scale clinical assessment of PPs to decrease the consequences of AFs is highly required.
Antidiabetic activity of Solanum torvum fruit extract in streptozotocin-induced diabetic rats
Authors: Satyanarayana Namani , Chinni Suresh V. , Gobinath Ramachawolran , Sunitha Paripelli , Uma Sankar Akula , Muthuvenkatachalam Bala Sundaram
Published: October 2022

Background

Solanum torvumSwartz, a medicinal plant belonging to the family Solanaceae, is an important medicinal plant widely distributed throughout the world and used as medicine to treat diabetes, hypertension, tooth decay, and reproductive problems in traditional systems of medicine around the world including Malaysia. The objective of this study was to investigate hypoglycemic, antilipidemic, and hepatoprotective activities, histopathology of the pancreas, and specific glucose regulating gene expression of the ethanolic extract ofS. torvumfruit in streptozotocin-induced diabetic Sprague–Dawley rats.

Materials and methods

Acute toxicity study was done according to OECD-423 guidelines. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in male Sprague–Dawley rats. Experimental diabetic rats were divided into six different groups; normal, diabetic control, and glibenclamide at 6 mg/kg body weight, and the other three groups of animals were treated with oral administration of ethanolic extract ofS. torvumfruit at 120, 160, and 200 mg/kg for 28 days. The effect of ethanolic extract ofS. torvumfruit on body weight, blood glucose, lipid profile, liver enzymes, histopathology of pancreas, and gene expression of glucose transporter 2 (slc2a2), and phosphoenolpyruvate carboxykinase (PCK1) was determined by RT-PCR.

Results

Acute toxicity studies showed LD50of ethanolic extract ofS. torvumfruit to be at the dose of 1600 mg/kg body weight. Blood glucose, total cholesterol, triglycerides, low-density lipoproteins, very low-density lipoproteins, serum alanine aminotransferase, and aspartate aminotransferase were significantly reduced, whereas high-density lipoproteins were significantly increased inS. torvumfruit (200 mg/kg)-treated rats. Histopathological study of the pancreas showed an increase in number, size, and regeneration of β-cell of islets of Langerhans. Gene expression studies revealed the lower expression ofslc2a2andPCK1in treated animals when compared to diabetic control.

Conclusion

Ethanolic extract ofS. torvumfruits showed hypoglycemic, hypolipidemic, and hepatoprotective activity in streptozocin-induced diabetic rats. Histopathological studies revealed regeneration of β cells of islets of Langerhans. Gene expression studies indicated lower expression ofslc2a2andPCK1in treated animals when compared to diabetic control, indicating that the treated animals prefer the gluconeogenesis pathway.
Potential bioactivity of Phoenix dactylifera fruits, leaves, and seeds against prostate and pancreatic cancer cells
Authors: Ghazzawy Hesham S. , Gouda Mostafa M. , Awad Nabil S. , Al-Harbi Nadi Awad , Alqahtani Mesfer M. , Abdel-Salam Maha M. , Abdein Mohamed A. , Al-Sobeai Sanad M. , Hamad Asmaa A. , Alsberi Hassan M. , Gabr Gamal A. , Hikal Dalia M.
Published: October 2022

The use of functional foods’ phytochemicals in the chemoprevention of different cancer diseases has become one of the hot scientific areas in the clinical nutrition field. For instance, the Khalas palm cultivar (KPC; Phoenix dactylifera) is one of the natural sustainable resources that have high bioactivity and functionality. This study aimed to investigate the antiproliferative activity and mode of action of KPC’s different parts on prostate (Pc3) and pancreatic (panc1) cancer cells at a molecular level. In the methods, KPC’s leaves, seeds, and fruits’ chemical composition and phytochemical analysis were analyzed. Also, the cytotoxic effects of each extract were assessed against pc3 and panc1 cell lines. Besides, induction of apoptosis, cell cycle analysis, and gene expression of both Cap3 and Cap9 were studied. The obtained results indicated that KPC leaves extract exhibited the highest significant (P < 0.01) anti-proliferation activity against the utilized cancer cell lines compared to fruits and seeds extracts. Also, there were significant (P < 0.05) differences in the phenolic contents, flavonoid of compounds, and antioxidant power of the leaves when compared to the seeds and fruits. Additionally, the highest cytotoxic effect (lowest IC50) was recorded with leave extract than seeds and fruits. Meanwhile, the seeds extract induced (P < 0.05) the apoptosis and arrested cells in the G2/M phase as well as up-regulated the gene expression of the apoptotic-related genes (Casp3 and Casp9) compared to the control group. In conclusion, this study showed that the presence of bioactive components in the KPC different parts extracts have the significant ability to induce the apoptotic pathway that could down-regulate the proliferation of prostate (pc3) and pancreatic (panc1) cancer cells. The pathway mechanism of action was induced by the phytol molecule presented in its leaves extract.
ALDH1: A potential therapeutic target for cancer stem cells in solid tumors
Authors: Wei Yaolu , Li Yan , Chen Yenan , Liu Pei , Huang Sheng , Zhang Yuping , Sun Yanling , Wu Zhe , Hu Meichun , Wu Qian , Wu Hongnian , Liu Fuxing , She Tonghui , Ning Zhifeng
Published: October 2022

Solid tumors can be divided into benign solid tumors and solid malignant tumors in the academic community, among which malignant solid tumors are called cancers. Cancer is the second leading cause of death in the world, and the global incidence of cancer is increasing yearly New cancer patients in China are always the first. After the concept of stem cells was introduced in the tumor community, the CSC markers represented by ALDH1 have been widely studied due to their strong CSC cell characteristics and potential to be the driving force of tumor metastasis. In the research results in the past five years, it has been found that ALDH1 is highly expressed in various solid cancers such as breast cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer, cervical cancer, esophageal cancer, ovarian cancer, head,and neck cancer. ALDH1 can activate and transform various pathways (such as the USP28/MYC signaling pathway, ALDH1A1/HIF-1α/VEGF axis, wnt/β-catenin signaling pathway), as well as change the intracellular pH value to promote formation and maintenance, resulting in drug resistance in tumors. By targeting and inhibiting ALDH1 in tumor stem cells, it can enhance the sensitivity of drugs and inhibit the proliferation, differentiation, and metastasis of solid tumor stem cells to some extent. This review discusses the relationship and pathway of ALDH1 with various solid tumors. It proposes that ALDH1 may serve as a diagnosis and therapeutic target for CSC, providing new insights and new strategies for reliable tumor treatment.
Prediction of single pulmonary nodule growth by CT radiomics and clinical features — a one-year follow-up study
Authors: Yang Ran , Hui Dongming , Li Xing , Wang Kun , Li Caiyong , Li Zhichao
Published: October 2022

Background

With the development of imaging technology, an increasing number of pulmonary nodules have been found. Some pulmonary nodules may gradually grow and develop into lung cancer, while others may remain stable for many years. Accurately predicting the growth of pulmonary nodules in advance is of great clinical significance for early treatment. The purpose of this study was to establish a predictive model using radiomics and to study its value in predicting the growth of pulmonary nodules.

Materials and methods

According to the inclusion and exclusion criteria, 228 pulmonary nodules in 228 subjects were included in the study. During the one-year follow-up, 69 nodules grew larger, and 159 nodules remained stable. All the nodules were randomly divided into the training group and validation group in a proportion of 7:3. For the training data set, the t test, Chi-square test and Fisher exact test were used to analyze the sex, age and nodule location of the growth group and stable group. Two radiologists independently delineated the ROIs of the nodules to extract the radiomics characteristics using Pyradiomics. After dimension reduction by the LASSO algorithm, logistic regression analysis was performed on age and ten selected radiological features, and a prediction model was established and tested in the validation group. SVM, RF, MLP and AdaBoost models were also established, and the prediction effect was evaluated by ROC analysis.

Results

There was a significant difference in age between the growth group and the stable group (P < 0.05), but there was no significant difference in sex or nodule location (P > 0.05). The interclass correlation coefficients between the two observers were > 0.75. After dimension reduction by the LASSO algorithm, ten radiomic features were selected, including two shape-based features, one gray-level-cooccurence-matrix (GLCM), one first-order feature, one gray-level-run-length-matrix (GLRLM), three gray-level-dependence-matrix (GLDM) and two gray-level-size-zone-matrix (GLSZM). The logistic regression model combining age and radiomics features achieved an AUC of 0.87 and an accuracy of 0.82 in the training group and an AUC of 0.82 and an accuracy of 0.84 in the verification group for the prediction of nodule growth. For nonlinear models, in the training group, the AUCs of the SVM, RF, MLP and boost models were 0.95, 1.0, 1.0 and 1.0, respectively. In the validation group, the AUCs of the SVM, RF, MLP and boost models were 0.81, 0.77, 0.81, and 0.71, respectively.

Conclusions

In this study, we established several machine learning models that can successfully predict the growth of pulmonary nodules within one year. The logistic regression model combining age and imaging parameters has the best accuracy and generalization. This model is very helpful for the early treatment of pulmonary nodules and has important clinical significance.
How cancer patients get fake cancer information: From TV to YouTube, a qualitative study focusing on fenbendazole scandle
Authors: Kim Jee Hyun , Oh Kyoung Hee , Shin Hye Young , Jun Jae Kwan
Published: October 2022

Background

Korean society has faced challenges in communicating with cancer patients about false information related to complementary alternative medicine. As the situation has become severe with the 2020 fenbendazole scandal, the demand for reliable information from health authorities has increased.

Objectives

This study aimed to examine patients’ acquisition patterns and perception of false information by presenting empirical evidence to help health authorities enable effective preemptive responses in the cancer communication context.

Method

We conducted a focus group interview with 21 lung cancer patients who were informed about fenbendazole based on a semi-structured questionnaire with three categories: 1) acquisition channel of the general cancer information and the false information, 2) quality of obtained information, and 3) perception toward it. The interviewees, comprising 13 men and eight women, were aged 50 or older. Participants’ current stages of cancer were stages one, three, and four and there were seven people in each stage.

Results

1) Acquisition channel: Participants had their first encounter with false information through the TV, while the channels to obtain general cancer information were through Internet communities or portal sites. YouTube was a second channel to actively search for information regardless of the information type. 2) Information quality: participants had only fragmented information through media. 3) Perception: Most patients had a negative attitude toward complementary and alternative medicine information such as fenbendazole. They perceive that it needs to be verified by experts and filtered according to their arbitrary criteria. They had vague expectations based on a hope for “what if” at the same time.

Conclusions

Despite the complex media environment, traditional or legacy media is an important channel to encounter information. YouTube is independent of other media as an “active” information-seeking channel. Patients required the appropriate intervention of experts and governments because they perceived that they had obtained irrational and unreliable information from the media. Suggestions are made about how health authorities can construct an effective communication system focusing on the user to prevent patients from getting false cancer information.
A combined approach of robot-assisted laparoscopic pyeloplasty and flexible endoscopy to treat concomitant ureteropelvic junction obstruction and calyceal stones in children: Technical considerations and review of the literature
Authors: Wong Yuenshan Sammi , Lo Ka Lun , Pang Kristine Kit Yi , Tam Yuk Him
Published: October 2022

The management of children with concomitant ureteropelvic junction (UPJ) obstruction and calyceal stones remains challenging. The various treatment options available for pediatric nephrolithiasis may require multiple sessions, and the techniques by themselves are not designed for simultaneous correction of UPJ obstruction. Recently, success in combining robot-assisted laparoscopic pyeloplasty (RALP) and flexible endoscopy has been reported by multi-institutional studies to treat children with concomitant UPJ obstruction and renal stones. Given the paucity of technical details of this novel approach in the existing literature, we herein report our techniques to treat two girls aged 6 and 10 years who had concomitant UPJ obstruction and multiple stones in mid- and lower poles calyces. Three robotic ports were used without any assistant ports. A flexible endoscope, either a cystoscope or a single-use ureteroscope, was introduced via the undocked epigastric port to perform nephroscopy and stones removal after the renal pelvis was opened. The rest of the RALP was completed in the usual manner. Technical modifications were employed to facilitate the flexible endoscope to examine the entire calyceal system. Both patients underwent successful surgical procedures by the combined approach without any intra- or post-operative complications. Three and 14 stones were removed from each of the patients respectively. Postoperative investigations demonstrated successful correction of UPJ obstruction and complete stone clearance in both patients. A combined approach of RALP and flexible endoscopy is a safe and effective technique to treat concurrent UPJ obstruction and calyceal stones in children.
Ginsenoside Rc attenuates DSS-induced ulcerative colitis, intestinal inflammatory, and barrier function by activating the farnesoid X receptor
Authors: Tang Kaijia , Kong Danli , Peng Yuan , Guo Jingyi , Zhong Yadi , Yu Haibing , Mai Zhenhua , Chen Yanling , Chen Yingjian , Cui Tianqi , Duan Siwei , Li Tianyao , Liu Naihua , Zhang Dong , Ding Yuanlin , Huang Jiawen
Published: October 2022

Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling.

Materials and Methods:In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR−/-) mice were used for further validation.

Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1β, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1β, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR−/- mice.

Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.
The role of the type 7 adenylyl cyclase isoform in alcohol use disorder and depression
Authors: Tabakoff Boris , Hoffman Paula L.
Published: October 2022

The translation of extracellular signals to intracellular responses involves a number of signal transduction molecules. A major component of this signal transducing function is adenylyl cyclase, which produces the intracellular “second messenger,” cyclic AMP. What was initially considered as a single enzyme for cyclic AMP generation is now known to be a family of nine membrane-bound enzymes, and one cytosolic enzyme. Each member of the adenylyl cyclase family is distinguished by factors that modulate its catalytic activity, by the cell, tissue, and organ distribution of the family members, and by the physiological/behavioral functions that are subserved by particular family members. This review focuses on the Type 7 adenylyl cyclase (AC7) in terms of its catalytic characteristics and its relationship to alcohol use disorder (AUD, alcoholism), and major depressive disorder (MDD). AC7 may be part of the inherited system predisposing an individual to AUD and/or MDD in a sex-specific manner, or this enzyme may change in its expression or activity in response to the progression of disease or in response to treatment. The areas of brain expressing AC7 are related to responses to stress and evidence is available that CRF1 receptors are coupled to AC7 in the amygdala and pituitary. Interestingly, AC7 is the major form of the cyclase contained in bone marrow-derived cells of the immune system and platelets, and in microglia. AC7 is thus, poised to play an integral role in both peripheral and brain immune function thought to be etiologically involved in both AUD and MDD. Both platelet and lymphocyte adenylyl cyclase activity have been proposed as markers for AUD and MDD, as well as prognostic markers of positive response to medication for MDD. We finish with consideration of paths to medication development that may selectively modulate AC7 activity as treatments for MDD and AUD.
Ginkgolide C slows the progression of osteoarthritis by activating Nrf2/HO-1 and blocking the NF-κB pathway
Authors: Ma Tianwen , Jia Lina , Zhao Jinghua , Lv Liangyu , Yu Yue , Ruan Hongri , Song Xiaopeng , Chen Hong , Li Xin , Zhang Jiantao , Gao Li
Published: October 2022

Osteoarthritis (OA) is driven by chronic low-grade inflammation and subsequent cartilage degradation. OA is the most prevalent degenerative joint disease worldwide, and its treatment remains a challenge. The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of ginkgolide C (GC). Protective effects of GC on hydrogen peroxide (H2O2)-treated rat chondrocytes were evaluated using ELISA, qPCR, western blot analysis, flow cytometry, ROS detection and immunofluorescence in vitro. Ameliorating effects of GC on cartilage degeneration in rats were evaluated through behavioral assays, microcomputed tomography, histopathological analysis, western blot analysis and ELISA in vivo. In vitro, GC treatment inhibited the release of pro-apoptotic factors induced by H2O2 and promoted the release of the anti-apoptotic proteins. In addition, GC decreased the expression of matrix metalloproteinase (MMP3 and MMP13), thrombospondin motifs 4 (ADAMTS4), and inflammatory mediators inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and SOX9 thereby inhibiting extracellular matrix (ECM) degradation. Mechanistically, GC exerts its anti-apoptotic and anti-inflammatory effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, In a rat model with post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT), GC inhibited joint pain, cartilage destruction, and abnormal bone remodeling of subchondral bone. GC inhibited H2O2-induced chondrocyte apoptosis through Nrf2/HO-1 and NF-κB axis, exerted anti-inflammatory effects, and inhibited cartilage degeneration in rat OA. Our findings advanced the concept that GC may contribute to cartilage metabolism through anti-inflammatory and anti-apoptotic effects, and the identified GC is a potential therapeutic agent for the treatment of OA.
Nanosystems for chemodynamic based combination therapy: Strategies and recent advances
Authors: Li Minghui , Zhang Wen , Xu Xiaopeng , Liu Guoying , Dong Mengfei , Sun Kaoxiang , Zhang Peng
Published: October 2022

Chemodynamic therapy (CDT), a newly developed approach for cancer treatment, can convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (•OH) by using Fenton/Fenton-like reaction to kill tumor cells. However, due to the complexity of the intracellular environment of tumor cells, the therapeutic efficacy of CDT was severely restricted. Recently, combination therapy strategies have become popular approaches for tumor treatment, and there are numerous studies have demonstrated that the CDT-based combination strategies can significantly improve the anti-tumor efficiency of CDT. In this review, we outline some of the recent progress in cancer chemodynamic therapy from 2020, and discuss the progress in the design of nanosystems for CDT synergistic combination therapies.
Pharmacologic therapies of ARDS: From natural herb to nanomedicine
Authors: Meng Linlin , Liao Ximing , Wang Yuanyuan , Chen Liangzhi , Gao Wei , Wang Muyun , Dai Huiling , Yan Na , Gao Yixuan , Wu Xu , Wang Kun , Liu Qinghua
Published: October 2022

Acute respiratory distress syndrome (ARDS) is a common critical illness in respiratory care units with a huge public health burden. Despite tremendous advances in the prevention and treatment of ARDS, it remains the main cause of intensive care unit (ICU) management, and the mortality rate of ARDS remains unacceptably high. The poor performance of ARDS is closely related to its heterogeneous clinical syndrome caused by complicated pathophysiology. Based on the different pathophysiology phases, drugs, protective mechanical ventilation, conservative fluid therapy, and other treatment have been developed to serve as the ARDS therapeutic methods. In recent years, there has been a rapid development in nanomedicine, in which nanoparticles as drug delivery vehicles have been extensively studied in the treatment of ARDS. This study provides an overview of pharmacologic therapies for ARDS, including conventional drugs, natural medicine therapy, and nanomedicine. Particularly, we discuss the unique mechanism and strength of nanomedicine which may provide great promises in treating ARDS in the future.
Acetyl coenzyme A kinetic studies on N-acetylation of environmental carcinogens by human N-acetyltransferase 1 and its NAT1*14B variant
Authors: Habil Mariam R. , Doll Mark A. , Hein David W.
Published: October 2022

N-acetyltransferase 1 (NAT1) is a xenobiotic metabolizing enzyme that uses acetyl coenzyme A (AcCoA) as a cofactor for N-acetylation of many carcinogens including aromatic amines and alkylanilines. NAT1 is characterized by single nucleotide polymorphisms (SNPs) that may modulate affinity towards AcCoA. In the current study, we used Chinese hamster ovary (CHO) cells stably transfected with human NAT1*4 (reference allele) or NAT1*14B (variant allele) to measure AcCoA kinetic parameters for N-acetyltransferase activity measurements towards p-aminobenzoic acid (PABA), 4-aminobiphenyl (4-ABP), β-naphthylamine (BNA), benzidine and 3,4-dimethylaniline (3,4-DMA). Our results showed higher N-acetylation rates for each substrate catalyzed by NAT1*4 compared to NAT1*14B. NAT1*4 exhibited higher affinity to AcCoA when catalyzing the N-acetylation of BNA and benzidine compared to NAT1*14B. The results of the current study provide further insights into differences in carcinogen metabolism among individuals possessing the NAT1*14B haplotype.
Extract of Mallotus oppositifolius (Geiseler) Müll. Arg. increased prefrontal cortex dendritic spine density and serotonin and attenuated para-chlorophenylalanine-aggravated aggressive and depressive behaviors in mice
Authors: Kukuia Kennedy K.E. , Appiah Frimpong , Dugbartey George J. , Takyi Yaw F. , Amoateng Patrick , Amponsah Seth K. , Adi-Dako Ofosua , Koomson Awo E. , Ayertey Frederick , Adutwum-Ofosu Kevin K.
Published: October 2022

Background/Aim:Depression-related aggression is linked to serotonin (5-HT) and dendritic spine alterations. AlthoughMallotus oppositifoliusextract (MOE) has potential for reducing this effect, its specific role remains uncertain. Herein, we evaluated this potential and associated alterations in the brain.

Methods:A standard resident-intruder model ofpara-chlorophenylalanine (pCPA)-induced depression-associated aggression in male ICR mice was used. The resident mice receivedpCPA (300 mg/kg, i. p.) for 3 consecutive days while saline-treated mice served as negative control. ThepCPA aggressive mice were subsequently treated orally with either MOE (30, 100, 300 mg/kg), fluoxetine (20 mg/kg), tryptophan (20 mg/kg) or saline (untreatedpCPA group) for 28 days. Locomotor activity was assessed using open field test. Serotonin (5-HT) levels in mice brain and phytochemical fingerprint of MOE were determined by high performance liquid chromatography (HPLC) while gas chromatography-mass spectrometry (GC-MS) was used to identify constituents of MOE. Dendritic spine density and morphology were evaluated using Golgi-Cox staining technique and analyzed with ImageJ and Reconstruct software.

Results:Administration ofpCPA induced aggressive behavior in mice, evidenced by increased attack behaviors (increased number and duration of attacks), which positively correlated with squeaking and tail rattling. MOE treatment significantly reduced these characteristics of aggression in comparison with vehicle (non-aggressive) and untreatedpCPA groups (p< 0.001), and also reduced social exploration behavior. Although the behavioral effects of MOE were comparable to those of fluoxetine and tryptophan, these effects were quicker compared to fluoxetine and tryptophan. Additionally, MOE also markedly increased 5-HT concentration and dendritic spine density in the prefrontal cortex relative to vehicle and untreatedpCPA groups (p< 0.05). Interestingly, these behavioral effects were produced without compromising locomotor activity. GC-MS analysis of the MOE identified 17 known compounds from different chemical classes with anti-inflammatory, antioxidant, neuroprotective and antidepressant activities, which may have contributed to its anti-aggressive effect.

Conclusion:MOE decreased depression-associated aggressive behavior in miceviaincreased 5-HT concentration and dendritic spine density in the prefrontal cortex. The MOE-mediated effects were faster than those of fluoxetine and tryptophan. Our finding suggests that MOE may have clinical promise in decreasing aggressive and depressive behaviors.
Differentiation and on axon-guidance chip culture of human pluripotent stem cell-derived peripheral cholinergic neurons for airway neurobiology studies
Authors: Goldsteen P. A. , Sabogal Guaqueta A. M. , Mulder P. P. M. F. A. , Bos I. S. T. , Eggens M. , Van der Koog L. , Soeiro J. T. , Halayko A. J. , Mathwig K. , Kistemaker L. E. M. , Verpoorte E. M. J. , Dolga A. M. , Gosens R.
Published: October 2022

Airway cholinergic nerves play a key role in airway physiology and disease. In asthma and other diseases of the respiratory tract, airway cholinergic neurons undergo plasticity and contribute to airway hyperresponsiveness and mucus secretion. We currently lack human in vitro models for airway cholinergic neurons. Here, we aimed to develop a human in vitro model for peripheral cholinergic neurons using human pluripotent stem cell (hPSC) technology. hPSCs were differentiated towards vagal neural crest precursors and subsequently directed towards functional airway cholinergic neurons using the neurotrophin brain-derived neurotrophic factor (BDNF). Cholinergic neurons were characterized by ChAT and VAChT expression, and responded to chemical stimulation with changes in Ca2+ mobilization. To culture these cells, allowing axonal separation from the neuronal cell bodies, a two-compartment PDMS microfluidic chip was subsequently fabricated. The two compartments were connected via microchannels to enable axonal outgrowth. On-chip cell culture did not compromise phenotypical characteristics of the cells compared to standard culture plates. When the hPSC-derived peripheral cholinergic neurons were cultured in the chip, axonal outgrowth was visible, while the somal bodies of the neurons were confined to their compartment. Neurons formed contacts with airway smooth muscle cells cultured in the axonal compartment. The microfluidic chip developed in this study represents a human in vitro platform to model neuro-effector interactions in the airways that may be used for mechanistic studies into neuroplasticity in asthma and other lung diseases.
Forecasting changes of the magnetic field in the United Kingdom from L1 Lagrange solar wind measurements
Authors: Madsen Frederik Dahl , Beggan Ciarán D. , Whaler Kathryn A.
Published: October 2022

Extreme space weather events can have large impacts on ground-based infrastructure important to technology-based societies. Machine learning techniques based on interplanetary observations have proven successful as a tool for forecasting global geomagnetic indices, however, few studies have examined local ground magnetic field perturbations. Nowcast and forecast models which predict the magnitude of the horizontal geomagnetic field, |BH|, and its time derivative, dBHdt, at ground level would be valuable for assessing the potential space weather hazard. We attempt to predict the variation of the magnetic field at the three United Kingdom observatories (Eskdalemuir, Hartland and Lerwick) driven by L1 solar wind parameters. The horizontal magnetic field component and its time derivative are predicted from solar wind plasma and interplanetary magnetic field observations using Long Short-Term Memory (LSTM) networks and hybrid Convolutional Neural Network-LSTM models. A 5-fold grid search cross-validation is used for tuning the hyperparameters in each model. Forecasts were made with 5, 15 and 30-min lead times. Models were trained and validated with geomagnetic storm-only data from 1997 to 2016; their outputs were evaluated with the 7–9th September 2017 storms. The forecast models are only able to predict the directly driven parts of geomagnetic storms (not the substorms) and LSTM models generally perform best. We find the |BH| 15- and 30-min forecasts at Lerwick and Eskdalemuir have some predictive power. The 5-min |BH| forecast as well as all the dBHdt models for Eskdalemuir and all the Hartland models were found to have little or no predictive power. This suggests that the machine learning models have better forecasting power at higher latitude (closer to the auroral zones), where the ground magnetic variation field is larger and during storm onset, which is directly driven by changes in the solar wind.
Avian models for brain mechanisms underlying altered social behavior in autism
Authors: Csillag András , Ádám Ágota , Zachar Gergely
Published: October 2022

The current review is an update on experimental approaches in which birds serve as model species for the investigation of typical failure symptoms associated with autism spectrum disorder (ASD). The discussion is focused on deficiencies of social behavior, from social interactions of domestic chicks, based on visual and auditory cues, to vocal communication in songbirds. Two groups of pathogenetic/risk factors are discussed: 1) non-genetic (environmental/epigenetic) factors, exemplified by embryonic exposure to valproic acid (VPA), and 2) genetic factors, represented by a list of candidate genes and signaling pathways of diagnostic or predictive value in ASD patients. Given the similarities of birds as experimental models to humans (visual orientation, vocal learning, social cohesions), avian models usefully contribute toward the elucidation of the neural systems and developmental factors underlying ASD, improving the applicability of preclinical results obtained on laboratory rodents. Furthermore, they may predict potential susceptibility factors worthy of investigation (both by animal studies and by monitoring human babies at risk), with potential therapeutic consequence.
Ca2+ entry units in a superfast fish muscle
Authors: Kittelberger J. Matthew , Franzini-Armstrong Clara , Boncompagni Simona
Published: October 2022

Over the past two decades, mounting evidence has demonstrated that a mechanism known as store-operated Ca2+entry (SOCE) plays a crucial role in sustaining skeletal muscle contractility by facilitating Ca2+influx from the extracellular space during sarcoplasmic reticulum (SR) Ca2+depletion. We recently demonstrated that, in exercised fast-twitch muscle from mice, the incidence of Ca2+entry units (CEUs), newly described intracellular junctions between dead-end longitudinal transverse tubular (T-tubule) extensions and stacks of sarcoplasmic reticulum (SR) flat cisternae, strictly correlate with both the capability of fibers to maintain contractions during fatigue and enhanced Ca2+influxviaSOCE. Here, we tested the broader relevance of this result across vertebrates by searching for the presence of CEUs in the vocal muscles of a teleost fish adapted for extended, high-frequency activity. Specifically, we examined active vs. inactive superfast sonic muscles of plainfin midshipman (Porichthys notatus). Interestingly, muscles from actively humming territorial males had a much higher incidence of CEU SR stacks relative to territorial males that were not actively vocalizing, strengthening the concept that assembly of these structures is dynamic and use-dependent, as recently described in exercised muscles from mice. Our results support the hypothesis that CEUs represent a conserved mechanism, across vertebrates, for enabling high levels of repetitive muscle activity, and also provide new insights into the adaptive mechanisms underlying the unique properties of superfast midshipman sonic muscles.
Dose caffeinated energy drink is a consideration issue for endurance performance
Authors: Wang Jie-Ping , Wei Chen-Chan , Peng Yun-Dong , Wang Hsuan-Yun , Hung Chi-Hsiang , Hong Yin-Hui , Liou Yuh-Feng , Hou Chien-Wen
Published: October 2022

Caffeinated energy drinks are commonly taken to improve exercise performance, but there are few studies on the influence of different doses on an athlete’s performance. We conducted a double-blind, randomized, counter-balanced, and crossover research study to examine the effects of low caffeinated energy drink (Low ED) or high caffeinated energy drink (High ED) supplement on the performance, haematological response, and oxidative stress in triathletes. Twelve male participants underwent three testing sessions separated by weekly intervals, consisting of sprint triathlon training (0.75 km swim, 20 km cycle, and 5 km run). Before and during the trials, participants were randomly provided with either placebo (PLA) group, Low ED group, or High ED group. Exercise performance in the High ED group decreased significantly compared with the PLA and Low ED groups (p < 0.05). However, participants in the Low ED group also experienced an improved performance (p = 0.054). Analysis of variance revealed no differences among the three groups in cortisol and testosterone levels, or the Borg Rating of Perceived Exertion score (p > 0.5). Furthermore, superoxide dismutase (SOD) was reduced with exercise and were lowest in the High ED group. However, compared with PLA, a significant decrease of thiobarbituric acid reactive substances (TBARS) was observed in Low ED and High ED groups (p < 0.05). This indicates that caffeinated energy drink consumption may improve performance and reduce oxidative stress in sprint triathlon athletes. However, individual differences should be considered when supplementing with caffeinated energy drinks to decrease side effects.
Mineral nutrient dynamics in pecans (Carya illinoensis) ‘Mahan’ grown in southern China
Authors: Zhang Xiaodan , Chang Jun , Ren Huadong , Wu Yaopeng , Huang Mei , Wu Shuang , Yang Shuiping , Yao Xiaohua , Wang Kailiang
Published: October 2022

It is of great significance to study the nutritional characteristics of plants. Further understanding of plant mineral nutrient dynamics can provide theoretical basis for scientific fertilization to improve fruit quality and yield. In this study, eight mineral elements (N, P, K, Ca, Mg, Mn, Zn, B) were measured at regular intervals in leaves and kernels of the pecan “Mahan” planted in southern China. The study discussed the characteristics of mineral nutrient dynamics of pecan through the indicators of concentration, accumulation and cumulative relative rate, a new first proposed indicator, and focused on critical time, intensity, amount of mineral nutrients required in pecan during the fruit developing period, as well as the transfer information of the elements in leaves and kernels. The results show that the mineral nutrient requirements of the leaves and kernels are not identical, with an upward trend in nutrient accumulation within the kernel. The most abundant mineral nutrients in the leaves and kernels were N, K and Ca with Ca being greater than N in leaves. In particular, the concentration of Mn in pecan ‘Mahan’ is higher than that of other plants, and its Mg content is also higher than that of P in kernels. The dynamic changes of mineral nutrients in walnut showed obvious stages, with a trend of “slow (before mid-July) - fast (mid-July to late August) - slow (late August to late September) - fast (late September to harvest)”. The “critical period” of kernels was before mid-July, during which the cumulative relative rates increased rapidly, indicating that the kernels had a great potential to absorb mineral nutrients. Significant accumulation of mineral nutrients occurred from mid-July to late August and late September to the end.
Complete chloroplast genome sequences of Phlomis fruticosa and Phlomoides strigosa and comparative analysis of the genus Phlomis sensu lato (Lamiaceae)
Authors: Zhao Wei , Guo Lirong , Yang Yu , Wang Yan , Yang Li , Wei Cuimei , Guo Jian , Yan Kan , Chen Haijuan , Yang Zhigang , Li Yimeng
Published: October 2022

The taxonomic terms “Phlomis” and “Phlomoides” had been used to describe two sections within the genus Phlomis belonging to the Lamiaceae family. Recently, phylogenetic analyses using molecular markers showed that Phlomis and Phlomoides formed two monophyletic clades, and thus they are generally accepted as separate genera. In this study, we assembled the complete chloroplast genome of Phlomis fruticosa, which is the first reported chloroplast genome belonging to Phlomis genus, as well as the complete chloroplast genome of Phlomoides strigosa belonging to Phlomoides genus. The results showed that the length of chloroplast genome was 151,639 bp (Phlomis fruticosa) and 152,432 bp (Phlomoides strigosa), with conserved large single copy regions, small single copy regions, and inverted repeat regions. 121 genes in Phlomis fruticosa and 120 genes in Phlomoides strigosa were annotated. The chloroplast genomes of Phlomis fruticosa, Phlomoides strigosa, and three reported Phlomoides species, as well as those of 51 species from the Lamiaceae family, which covered 12 subfamilies, were subjected to phylogenetic analyses. The Phlomis and Phlomoides species were split into two groups, which were well supported by both maximum likelihood and Bayesian inference tree analyses. Our study provided further evidence to recognize Phlomis and Phlomoides as independent genera.