bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergence of biofilm successional trajectories initiated during contrasting seasons
Authors: Wang Jing , Peipoch Marc , Guo Xiaoxiao , Kan Jinjun
Published: September 2022

Biofilm communities play a major role in explaining the temporal variation of biogeochemical conditions in freshwater ecosystems, and yet we know little about how these complex microbial communities change over time (aka succession), and from different initial conditions, in comparison to other stream communities. This has resulted in limited knowledge on how biofilm community structure and microbial colonization vary over relevant time scales to become mature biofilms capable of significant alteration of the freshwater environment in which they live. Here, we monitored successional trajectories of biofilm communities from summer and winter in a headwater stream and evaluated their structural state over time by DNA high-throughput sequencing. Significant differences in biofilm composition were observed when microbial colonization started in the summer vs. winter seasons, with higher percentage of algae (Bacillariophyta) and Bacteroidetes in winter-initiated samples but higher abundance of Proteobacteria (e.g., Rhizobiales, Rhodobacterales, Sphingomonadales, and Burkholderiales), Actinobacteria, and Chloroflexi in summer-initiated samples. Interestingly, results showed that despite seasonal effects on early biofilm succession, biofilm community structures converged after 70 days, suggesting the existence of a stable, mature community in the stream that is independent of the environmental conditions during biofilm colonization. Overall, our results show that algae are important in the early development of biofilm communities during winter, while heterotrophic bacteria play a more critical role during summer colonization and development of biofilms.
Genomic and evolutionary characteristics of G9P[8], the dominant group a rotavirus in China (2016–2018)
Authors: Liu Xiafei , Wang Mengxuan , Li Shan , Li Jingxin , Xiao Jinbo , Li Huiying , Zhang Qing , Kong Xiangyu , Wang Hong , Li Dandi , Duan Zhaojun
Published: September 2022

G9P[8] became the predominant rotavirus A (RVA) genotype in China in 2012. To evaluate its genetic composition at the whole-genome level, 115 G9P[8] RVA strains isolated from children under 5 years old were sequenced and characterized. All 13 strains in 2016 and 2017 and an additional 54 strains in 2018 were genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. The other 48 strains in 2018 were all genotyped as G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1, with the NSP4 gene characterized as a DS-1-like genotype. The time of the most recent common ancestor (tMRCA) and evolution rates of the VP7, VP4, and NSP4 (E1 and E2) genes of these strains were estimated by Bayesian evolutionary dynamics analysis. We estimated the evolution rates (nt substitutions per site per year) as 1.38 × 10–3 [the 95% highest posterior density (HPD) was 1.09–1.72 × 10–3] for VP7, 0.87 × 10–3 (95% HPD: 0.75–1.00 × 10–3) for VP4, 0.56 × 10–3 (95% HPD: 0.41–0.73 × 10–3) for NSP4-E1, and 1.35 × 10–3 (95% HPD: 0.92–1.86 × 10–3) for NSP4-E2. The tMRCA was estimated to be 1935.4 (95% HPD: 1892.4–1961.3) for VP7, 1894.3 (95% HPD: 1850.5–1937.8) for VP4, 1929.4 (95% HPD: 1892.4–1961.3) for NSP4-E1, and 1969.2 (95% HPD: 1942.2–1985.3) for NSP4-E2. The baseline genetic information in this study is expected to improve our understanding of the genomic and evolutionary characteristics of the rotavirus genome. Furthermore, it will provide a basis for the development of next-generation rotavirus vaccines for humans.
Structural insights into the functional roles of 14-3-3 proteins
Authors: Obsilova Veronika , Obsil Tomas
Published: September 2022

Signal transduction cascades efficiently transmit chemical and/or physical signals from the extracellular environment to intracellular compartments, thereby eliciting an appropriate cellular response. Most often, these signaling processes are mediated by specific protein-protein interactions involving hundreds of different receptors, enzymes, transcription factors, and signaling, adaptor and scaffolding proteins. Among them, 14-3-3 proteins are a family of highly conserved scaffolding molecules expressed in all eukaryotes, where they modulate the function of other proteins, primarily in a phosphorylation-dependent manner. Through these binding interactions, 14-3-3 proteins participate in key cellular processes, such as cell-cycle control, apoptosis, signal transduction, energy metabolism, and protein trafficking. To date, several hundreds of 14-3-3 binding partners have been identified, including protein kinases, phosphatases, receptors and transcription factors, which have been implicated in the onset of various diseases. As such, 14-3-3 proteins are promising targets for pharmaceutical interventions. However, despite intensive research into their protein-protein interactions, our understanding of the molecular mechanisms whereby 14-3-3 proteins regulate the functions of their binding partners remains insufficient. This review article provides an overview of the current state of the art of the molecular mechanisms whereby 14-3-3 proteins regulate their binding partners, focusing on recent structural studies of 14-3-3 protein complexes.
Reduced plasma levels of RGM-A predict stroke-associated pneumonia in patients with acute ischemic stroke: A prospective clinical study
Authors: Zhong Jiaju , Liao Juan , Zhang Rongrong , Zhou Chanjuan , Wang Zhenyu , Huang Siyuan , Huang Dan , Yang Mengliu , Zhang Lei , Ma Yue , Qin Xinyue
Published: September 2022

Background

Stroke-induced immunodepression syndrome is considered the major etiology of stroke-associated pneumonia (SAP). Repulsive guidance molecule A (RGM-A) is an immunomodulatory protein that is closely related to inflammation and immune responses. To explore the relationship between RGM-A and SAP and facilitate the early identification of patients at high risk of developing SAP, we investigated the predictive value of RGM-A in SAP.

Methods

We enrolled 178 patients with acute ischemic stroke (AIS) and finally analyzed 150 patients, among whom 69 had SAP and 81 had non-SAP. During the same period, 40 patients with community-acquired pneumonia and 40 healthy participants were included as controls. SAP was defined according to the modified US Centers for Disease Control and Prevention criteria. Blood samples were collected at 24 h, 48 h, 3 days, 4 to 7 days, and 8 to 14 days after stroke onset. An enzyme-linked immunosorbent assay was used to detect the plasma levels of RGM-A and interleukin-6.

Results

The plasma RGM-A levels were significantly decreased in both patients with community-acquired pneumonia and those with AIS, and the decline was most pronounced in patients with SAP (P < 0.001). RGM-A started to decline within 24 h after stroke in the SAP group, and the lowest levels were detected on day 3 and days 4 to 7 (P < 0.001). The RGM-A levels in the SAP group were lower than those in the non-SAP group at all blood collection time points (P < 0.05). In the logistic regression analyses, RGM-A was a protective factor for SAP after adjusting for confounders (adjusted odds ratio = 0.22, 95% confidence interval = 0.091–0.538, P = 0.001). Receiver operating characteristic curve analysis showed that the area under the curve for RGM-A was 0.766 (0.091–0.538; P = 0.001), the cutoff value was 4.881 ng/mL, and the sensitivity and specificity were 80.00 and 76.36%, respectively.

Conclusions

We demonstrated that reduced plasma levels of RGM-A might help in the early identification of high-risk patients with SAP and predict the occurrence of SAP in patients with AIS. RGM-A might provide new clues to a potential alternative therapy for SAP.
Optical coherence tomography assessment of axonal and neuronal damage of the retina in patients with familial and sporadic multiple sclerosis
Authors: Grudziecka Pyrek Monika , Selmaj Krzysztof
Published: September 2022

Objective

To assess axonal and neuronal damage of the retina in patients with familial (fMS) and sporadic multiple sclerosis (sMS).

Methods

87 relapsing-remitting MS patients (45 patients with sMS, 42 patients with fMS) and 30 healthy controls were included in the study. Optical coherence tomography (OCT) was performed with the spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Germany). The peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, total macular volume (TMV) and the inner nuclear layer (INL) thickness were measured.

Results

A significant reduction of the pRNFL thickness was detected in sMS and fMS compared to the control group (86.29 (+/- 16.13) μm in sMS, 84.78 (+/- 12.92) μm in fMS, 98.93 (+/- 6.71) μm in control group; p < 0.001). There was no significant difference in the pRNFL thickness between sMS and fMS (p = 0.5239). The GCIPL thickness was significantly decreased in sMS and fMS compared to the control group [66.0581 (+/- 11.2674) μm in sMS, 63.8386 (+/-10.004) μm in fMS, 76.5074 (+/- 5.0004) μm in control group; p < 0.001]. A significant reduction of the TMV was shown in sMS and fMS compared to the control group [8.4541(+/- 0.4727) mm3 in sMS, 8.3612 (+/- 0.4448) mm3 in fMS, 8.8387 (+/- 0.314) mm3 in control group; p < 0.0011]. No difference in the GCIPL thickness and TMV between sMS and fMS was found (p = 0.3689 and p = 0.3758, respectively). The INL thickness in sMS and fMS did not differ compared to the control group [34.2323 (+/- 2.7006) μm in sMS, 34.5159 (+/- 2.9780) μm in fMS, 33.6148 (+/- 2.0811) μm in control group; p = 0.5971 and p = 0.1870, respectively] and between the two forms (p = 0.4894).

Conclusion

We confirmed the presence of axonal and neuronal damage of the retina in sMS and fMS. Both forms of MS did not differ significantly from each other with respect to RFNL, GCIPL, MV and INL. ON induced significant reduction of the pRNFL, GCIPL and MV in both groups of pwMS.
The sensitivity and specificity of the modified volume-viscosity swallow test for dysphagia screening among neurological patients
Authors: Lin Yiqiu , Wan Guifang , Wu Huixiang , Shi Jing , Zhang Yaowen , Chen Huayu , Wei Xiaomei , Tang Zhiming , Dai Meng , Dou Zulin , Wen Hongmei
Published: September 2022

Oropharyngeal dysphagia (OD) is a highly prevalent condition after stroke and other neurological diseases. The volume-viscosity swallow test (V-VST) is a screening tool for OD. Considering that the recommendations of volume and thickeners in the original V-VST limited the popularization and application of the test in the Chinese population, we provide the modified V-VST to detect OD among neurological patients. In addition, the accuracy of the modified V-VST to screen OD needs to be verified. We included 101 patients with neurological diseases. OD was evaluated by a modified V-VST and a videofluoroscopy swallowing study (VFSS) using 3 volumes (i.e., 3, 5, and 10 ml) and 4 viscosities (i.e., water, mildly thick, moderately thick, and extremely thick). In this study, to compare with the original V-VST results, a volume of 20 ml was also included. The discriminating ability of modified V-VST in detecting OD was assessed by the sensitivity and specificity values of clinical signs of impaired efficiency (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallowing (cough, voice changes, and oxygen desaturation ≥3%) in comparison to the results of VFSS. The modified V-VST showed 96.6% sensitivity and 83.3% specificity for OD, 85.2% sensitivity and 70% specificity for impaired safety, and 90.9% sensitivity and 76.9% specificity for impaired efficacy. Our study suggests that the modified V-VST offers a high discriminating ability in detecting OD among neurological patients.
Trigeminal neuralgia caused by cavernoma: A case report with literature review
Authors: Liu Hongyu , Chen Chuanbiao , Liu Yuyang , Liu Jialin , Yu Xinguang , Chen Ling
Published: September 2022

Cavernoma is the second most common cerebrovascular lesion. Cavernoma involving the cranial nerves is very rare. Only 15 cases of cavernoma presenting with trigeminal neuralgia (TN) have been previously reported. Here, we report a rare case of cavernoma manifesting with TN. A young female patient with a 15-day history of right-sided lancinating pain in the face, difficulty in opening the mouth, and hearing dysesthesia. Magnetic resonance imaging (MRI) revealed a well-demarcated lesion in the cerebellopontine angle related closely to the root of the trigeminal nerve. The initial impression was that of a neurinoma. The lesion was surgically resected via the retrosigmoid approach, postoperative pathological analysis confirmed the diagnosis of cavernoma, and the patient's pain and difficulty in opening the mouth resolved completely. We presented the 16th documented case of cavernoma with TN. Although cavernoma involving the trigeminal nerve is extremely rare, this diagnosis should be taken into consideration when a lesion in the cerebellopontine angle is detected on MRI, and the clinical manifestation is consistent with that of secondary TN. Specialized MRI sequences, such as susceptibility weighted imaging (SWI), gradient echo T2, and constructive interference in steady-state (CISS)-weighted imaging, aid in establishing the diagnosis. Resection via craniotomy may be the primary management strategy for cavernoma causing TN. In addition, gamma knife radiosurgery (GKRS) and percutaneous balloon compression (PBC) may ameliorate the pain to some extent.
Development and in vivo validation of small interfering RNAs targeting NOX3 to prevent sensorineural hearing loss
Authors: Nacher-Soler German , Marteyn Antoine , Barenzung Natasha , Sgroi Stéphanie , Krause Karl-Heinz , Senn Pascal , Rousset Francis
Published: September 2022

The reactive oxygen species (ROS)-generating enzyme NOX3 has recently been implicated in the pathophysiology of several acquired forms of sensorineural hearing loss, including cisplatin-, noise- and age-related hearing loss. NOX3 is highly and specifically expressed in the inner ear and therefore represents an attractive target for specific intervention aiming at otoprotection. Despite the strong rationale to inhibit NOX3, there is currently no specific pharmacological inhibitor available. Molecular therapy may represent a powerful alternative. In this study, we developed and tested a collection of small interfering (si) RNA constructs to establish a proof of concept of NOX3 inhibition through local delivery in the mouse inner ear. The inhibitory potential of 10 different siRNA constructs was first assessed in three different cells lines expressing the NOX3 complex. Efficacy of the most promising siRNA construct to knock-down NOX3 was then further assessed in vivo, comparing middle ear delivery and direct intracochlear delivery through the posterior semi-circular canal. While hearing was completely preserved through the intervention, a significant downregulation of NOX3 expression in the mouse inner ear and particularly in the spiral ganglion area at clinically relevant levels (>60%) was observed 48 h after treatment. In contrast to successful intracochlear delivery, middle ear administration of siRNA failed to significantly inhibit Nox3 mRNA expression. In conclusion, intracochlear delivery of NOX3-siRNAs induces a robust temporal NOX3 downregulation, which could be of relevance to prevent predictable acute insults such as cisplatin chemotherapy-mediated ototoxicity and other forms of acquired hearing loss, including post-prevention of noise-induced hearing loss immediately after trauma. Successful translation of our concept into an eventual clinical use in humans will depend on the development of atraumatic and efficient delivery routes into the cochlea without a risk to induce hearing loss through the intervention.
More than a marker: potential pathogenic functions of MAP2
Authors: DeGiosio Rebecca A. , Grubisha Melanie J. , MacDonald Matthew L. , McKinney Brandon C. , Camacho Carlos J. , Sweet Robert A.
Published: September 2022

Microtubule-associated protein 2 (MAP2) is the predominant cytoskeletal regulator within neuronal dendrites, abundant and specific enough to serve as a robust somatodendritic marker. It influences microtubule dynamics and microtubule/actin interactions to control neurite outgrowth and synaptic functions, similarly to the closely related MAP Tau. Though pathology of Tau has been well appreciated in the context of neurodegenerative disorders, the consequences of pathologically dysregulated MAP2 have been little explored, despite alterations in its immunoreactivity, expression, splicing and/or stability being observed in a variety of neurodegenerative and neuropsychiatric disorders including Huntington’s disease, prion disease, schizophrenia, autism, major depression and bipolar disorder. Here we review the understood structure and functions of MAP2, including in neurite outgrowth, synaptic plasticity, and regulation of protein folding/transport. We also describe known and potential mechanisms by which MAP2 can be regulated via post-translational modification. Then, we assess existing evidence of its dysregulation in various brain disorders, including from immunohistochemical and (phospho) proteomic data. We propose pathways by which MAP2 pathology could contribute to endophenotypes which characterize these disorders, giving rise to the concept of a “MAP2opathy”—a series of disorders characterized by alterations in MAP2 function.
Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis
Authors: Wang Kai , Yang Fangkun , Zhang Pengcheng , Yang Yang , Jiang Li
Published: September 2022

Background and aims

Although iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.

Methods

Independent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.

Results

Genetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.

Conclusion

Our study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified.
Intestinal permeability of agaro-oligosaccharides: Transport across Caco-2 cell monolayers and pharmacokinetics in rats
Authors: Shirai Ikuya , Karasawa Koji , Kodaira Yusuke , Iwasaki Yu , Shigemura Yasutaka , Makabe Hidefumi , Katayama Shigeru
Published: September 2022

Agaro-oligosaccharides (AOSs), even-numbered oligosaccharides prepared from agar, are applied to various food, including supplements, drinks, and jellies because of their biological activities. This study aimed to evaluate the AOS permeation in the gastrointestinal tract in vivo and in vitro. Agarobiose (Abi), agarotetraose (Ate), and agarohexaose (Ahe) were detected in rat plasma after oral administration of AOSs. The detection level of agarobiose in the plasma was higher than that of agarohexaose, which was consistent with the permeation study using Caco-2 cell monolayers. Further, the adenosine triphosphate inhibitor (sodium azide) or endocytosis inhibitor (colchicine) did not inhibit AOS permeation through Caco-2 cell monolayers. Conversely, AOS permeation enhanced upon treatment with cytochalasin B, a tight junction disrupter, suggesting that AOSs might have passed mainly through the tight junctions between the intestinal epithelial cells. These results indicate that AOSs, especially agarobiose, can be absorbed as an intact form via the gastrointestinal tract across the intestinal epithelium through the paracellular pathway.
Perspectives of lipid metabolism reprogramming in head and neck squamous cell carcinoma: An overview
Authors: Miao Xiangwan , Wang Beilei , Chen Kaili , Ding Rui , Wu Jichang , Pan Yi , Ji Peilin , Ye Bin , Xiang Mingliang
Published: September 2022

Recent studies showed that lipid metabolism reprogramming contributes to tumorigenicity and malignancy by interfering energy production, membrane formation, and signal transduction in cancers. HNSCCs are highly reliant on aerobic glycolysis and glutamine metabolism. However, the mechanisms underlying lipid metabolism reprogramming in HNSCCs remains obscure. The present review summarizes and discusses the “vital” cellular signaling roles of the lipid metabolism reprogramming in HNSCCs. We also address the differences between HNSCCs regions caused by anatomical heterogeneity. We enumerate these recent findings into our current understanding of lipid metabolism reprogramming in HNSCCs and introduce the new and exciting therapeutic implications of targeting the lipid metabolism.
The Impact of Malignancy on Assisted Reproductive Outcomes for Cancer Survivors: A Retrospective Case–Control Study
Authors: Li Yuehong , Cai Xuefen , Dong Binhua , Wang Qi , Yang Xiaohui , Yu Aili , Wei Huijuan , Ke Zhanghong , Sun Pengming , Zheng Beihong , Sun Yan
Published: September 2022

Background

Related studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes.

Methods

This retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes.

Results

This study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P<0.001) between the two groups. The total gonadotropin dose, number of oocytes retrieved, fertilization rate, cleavage rate, high-quality embryo rate, blastocyst rate and first-time embryo-transfer (ET) implantation rate were nonsignificantly lower in the cancer group than in the control group (P>0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes.

Conclusions

Overall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes.
Survival nomogram for different grades of gastric cancer patients based on SEER database and external validation cohort
Authors: Hu Lei , Yang Kang , Chen Yue , Sun Chenyu , Wang Xu , Zhu Shaopu , Yang Shiyi , Cao Guodong , Xiong Maoming , Chen Bo
Published: September 2022

Background

Influencing factors varied among gastric cancer (GC) for different differentiation grades which affect the prognosis accordingly. This study aimed to develop a nomogram to effectively identify the overall survival (OS).

Methods

Totally, 9,568 patients with GC were obtained from the SEER database as the training cohort and internal validation cohort. We then retrospectively enrolled patients diagnosed with GC to construct the external validation cohort from the First Affiliated Hospital of Anhui Medical University. The prognostic factors were integrated into the multivariate Cox regression to construct a nomogram. To test the accuracy of the model, we used the calibration curves, receiver operating characteristics (ROC) curves, C-index, and decision curve analysis (DCA).

Results

Race chemotherapy, tumor size, and other four factors were significantly associated with the prognosis of Grade III GC Patients. On this basis, we developed a nomogram. The discrimination of the nomogram revealed good prognostic accuracy The results of the area under the curve (AUC) calculated by ROC for five-year survival were 0.828 and 0.758 in the training set and external validation cohort, higher than that of the TNM staging system. The calibration plot revealed that the estimated risk was close to the actual risk. DCA also suggested an excellent predictive value of the nomogram. Similar results were obtained in Grade-I and Grade-II GC patients.

Conclusions

The nomogram developed in this study and other findings could help individualize the treatment of GC patients and assist clinicians in their shared decision-making with patients.
The role of colonic motility in low anterior resection syndrome
Authors: Varghese Chris , Wells Cameron I. , Bissett Ian P. , O’Grady Gregory , Keane Celia
Published: September 2022

Low anterior resection syndrome (LARS) describes the symptoms and experiences of bowel dysfunction experienced by patients after rectal cancer surgery. LARS is a complex and multifactorial syndrome exacerbated by factors such as low anastomotic height, defunctioning of the colon and neorectum, and radiotherapy. There has recently been growing awareness and understanding regarding the role of colonic motility as a contributing mechanism for LARS. It is well established that rectosigmoid motility serves an important role in coordinating rectal filling and maintaining continence. Resection of the rectosigmoid may therefore contribute to LARS through altered distal colonic and neorectal motility. This review evaluates the role of colonic motility within the broader pathophysiology of LARS and outlines future directions of research needed to enable targeted therapy for specific LARS phenotypes.
Phosphoproteomics reveals that cinobufotalin promotes intrahepatic cholangiocarcinoma cell apoptosis by activating the ATM/CHK2/p53 signaling pathway
Authors: Xia Zhili , Li Minzhen , Hu Meng , Lin Yanyan , Atteh Lawrence Lawer , Fu Wenkang , Gao Long , Bai Mingzhen , Huang Chongfei , Yue Ping , Liu Yu , Meng Wenbo
Published: September 2022

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor that originates from bile duct’s epithelial cells and is usually characterized by insidious symptoms and poor prognosis. Cinobufotalin (CB), an active ingredient obtained from the Traditional Chinese Medicine ChanSu, is purported to exhibit a wide range of antitumorigenic activities. However, the mechanism by which it achieves such pharmacological effects remains elusive. Here, we disclosed the mechanism of action by which CB inhibits ICC cells. Initial experiments revealed that the proliferation of RBE and HCCC-9810 cells was significantly inhibited by CB with IC50 values of 0.342 μM and 0.421 μM respectively. CB induced the expression of caspase-3 subsequently leading to the apoptosis of ICC cells. Phosphoproteomics revealed that the phosphorylation of many proteins associated with DNA damage response increased. Kinase-substrate enrichment analysis revealed that ATM was activated after CB treatment, while CDK1 was inactivated. Activated ATM increased p-CHK2-T68 and p-p53-S15, which promoted the expression of FAS, DR4 and DR5 and triggered cell apoptosis. In summary, this work reveals the role of CB in inducing DNA damage and cell apoptosis involved in the activation of the ATM/CHK2/p53 signaling pathway, and indicates that CB may serve as a chemotherapeutic drug candidate for ICC treatment.
Adult-onset hereditary myeloid malignancy and allogeneic stem cell transplantation
Authors: Toya Takashi , Harada Hironori , Harada Yuka , Doki Noriko
Published: September 2022

Hereditary myeloid malignancies, especially in adults or elderly persons, had been considered quite rare before the next-generation sequencing era; however, increased usage of clinical sequencing has revealed much higher prevalence of inherited myeloid malignancies. DDX41 and various pathogenic germline mutations have newly been recognized as the cause of adult-onset familial leukemia and myeloid malignancies. Although germline predisposition to myeloid neoplasms had been categorized as a provisional entity in the World Health Organization classification of hematopoietic neoplasms in 2016, methodology for the identification of hereditary myeloid malignancies has not been fully established yet. In addition, many unresolved problems, such as epidemiology, the exact pathogenic mechanisms, and ideal treatment strategy, including indications of allogeneic hematopoietic stem cell transplantation, still remain. Related donor selection for stem cell transplant is a particularly sensitive issue due to the possibility of germline mutation of the candidate relatives and the risk of donor cell leukemia after transplantation. Here, we reviewed the current evidence regarding epidemiology, diagnosis, mechanisms of progression, and transplantation strategy for hereditary myeloid malignancies.
Monitoring disease progression in childhood bronchiectasis
Authors: Ramsey Kathryn A. , Schultz André
Published: September 2022

Bronchiectasis (not related to cystic fibrosis) is a chronic lung disease caused by a range of etiologies but characterized by abnormal airway dilatation, recurrent respiratory symptoms, impaired quality of life and reduced life expectancy. Patients typically experience episodes of chronic wet cough and recurrent pulmonary exacerbations requiring hospitalization. Early diagnosis and management of childhood bronchiectasis are essential to prevent respiratory decline, optimize quality of life, minimize pulmonary exacerbations, and potentially reverse bronchial disease. Disease monitoring potentially allows for (1) the early detection of acute exacerbations, facilitating timely intervention, (2) tracking the rate of disease progression for prognostic purposes, and (3) quantifying the response to therapies. This narrative review article will discuss methods for monitoring disease progression in children with bronchiectasis, including lung imaging, respiratory function, patient-reported outcomes, respiratory exacerbations, sputum biomarkers, and nutritional outcomes.
Potential role of MAP2K1 mutation in the trans-differentiation of interdigitating dendritic cell sarcoma: Case report and literature review
Authors: Jenei Alex , Bedics Gábor , Erdélyi Dániel J. , Müller Judit , Györke Tamás , Bödör Csaba , Szepesi Ágota
Published: September 2022

A 5-year-old male child was diagnosed with interdigitating dendritic cell sarcoma (IDCS) during his maintenance therapy for B-cell precursor acute lymphoblastic leukemia (B-ALL). Multiplex lymph node involvements of the neck were found by positron emission tomography CT (PET-CT). Treatments, including surgical and chemotherapy, resulted in complete remission. Four years later, systemic bone infiltration was discovered. Surgical resection of the IV rib and intensive chemotherapy led to a complete morphological remission, and allogeneic bone marrow transplantation was performed. Comprehensive genomic profiling of the formalin fixed the tumor tissue, and the cryopreserved leukemic cells revealed several common alterations and divergent clonal evolution with a novel MAP2K1 mutation of the IDCS, which is responsible for the trans-differentiation of the common lymphoid-committed tumor progenitor.
Imaging in children with ataxia-telangiectasia—The radiologist’s approach
Authors: Jończyk-Potoczna Katarzyna , Potoczny Jakub , Szczawińska-Popłonyk Aleksandra
Published: September 2022

Ataxia-telangiectasia (A-T) is a syndromic inborn error of immunity (IEI) characterized by genomic instability, defective reparation of the DNA double-strand breaks, and hypersensitivity to ionizing radiation disturbing cellular homeostasis. The role of imaging diagnostics and the conscious choice of safe and advantageous imaging technique, as well as its correct interpretation, are crucial in the diagnostic process and monitoring of children with A-T. This study aimed at defining the role of a radiologist in the early diagnosis of A-T, as well as in detecting and tracking disease complications associated with infections, inflammation, lymphoproliferation, organ-specific immunopathology, and malignancy. Based on our single-center experience, retrospective analysis of investigations using ionizing radiation-free techniques, ultrasound (US), and Magnetic Resonance Imaging (MRI), was performed on regularly followed-up 11 pediatric A-T patients, 6 girls and 5 boys, aged from 2 to 18 years, with the longest period of observation coming to over 13 years. Our attention was especially drawn to the abnormalities that were observed in the US and MRI examinations of the lungs, abdominal cavity, and lymph nodes. The abdominal US showed no abnormalities in organ dimensions or echostructure in 4 out of 11 children studied, yet in the other 7, during follow-up examinations, hepato- and/or splenomegaly, mesenteric, visceral, and paraaortic lymphadenopathy were observable. In 2 patients, focal changes in the liver and spleen were shown, and in one patient progressive abdominal lymphadenopathy corresponded with the diagnosis of non-Hodgkin lymphoma (NHL). The lung US revealed multiple subpleural consolidations and B line artifacts related to the interstitial-alveolar syndrome in 5 patients, accompanied by pleural effusion in one of them. The MRI investigation of the lung enabled the detection of lymphatic nodal masses in the mediastinum, with concomitant airway lesions characteristic of bronchiectasis and focal parenchymal consolidations in one A-T patient with chronic respiratory failure. This patient also manifested organomegaly and granulomatous liver disease in abdominal MRI examination. Our study shows that the use of modern US capabilities and MRI is safe and efficient, thereby serving as a recommended advantageous imaging diagnostic tool in monitoring children with IEI and DNA instability syndromes.
Natural flavonoids: Potential therapeutic strategies for non-alcoholic fatty liver disease
Authors: Tan Panli , Jin Li , Qin Xiang , He Beihui
Published: September 2022

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly worldwide; however, there are currently limited treatments for NAFLD. The disease spectrum includes simple fatty liver, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and progression to hepatocellular carcinoma (NASH-HCC). The therapeutic effects of NAFLD remain controversial. Although researchers have conducted studies on the pathogenesis of NAFLD, its pathogenesis and anti-NAFLD mechanisms have not been fully elucidated. Previous studies have found that flavonoids, as natural substances with extensive pharmacological activity and good therapeutic effects, have excellent antioxidant, anti-inflammatory, metabolic disease improvement, anti-tumor, and other properties and can significantly alleviate NAFLD. Flavonoids could be further developed as therapeutic drugs for NAFLD. In this paper, the pathogenesis of NAFLD and the mechanisms of flavonoids against NAFLD are summarized to provide a theoretical basis for screening flavonoids against non-alcoholic liver injury.
Potential therapeutic effects and pharmacological evidence of sinomenine in central nervous system disorders
Authors: Hong Hongxiang , Lu Xu , Lu Qun , Huang Chao , Cui Zhiming
Published: September 2022

Sinomenine is a natural compound extracted from the medicinal plant Sinomenium acutum. Its supplementation has been shown to present benefits in a variety of animal models of central nervous system (CNS) disorders, such as cerebral ischemia, intracerebral hemorrhage, traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, depression, multiple sclerosis, morphine tolerance, and glioma. Therefore, sinomenine is now considered a potential agent for the prevention and/or treatment of CNS disorders. Mechanistic studies have shown that inhibition of oxidative stress, microglia- or astrocyte-mediated neuroinflammation, and neuronal apoptosis are common mechanisms for the neuroprotective effects of sinomenine. Other mechanisms, including activation of nuclear factor E2-related factor 2 (Nrf2), induction of autophagy in response to inhibition of protein kinase B (Akt)-mammalian target of rapamycin (mTOR), and activation of cyclic adenosine monophosphate-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), may also mediate the anti-glioma and neuroprotective effects of sinomenine. Sinomenine treatment has also been shown to enhance dopamine receptor D2 (DRD2)-mediated nuclear translocation of αB-crystallin (CRYAB) in astrocytes, thereby suppressing neuroinflammation via inhibition of Signal Transducer and Activator of Transcription 3 (STAT3). In addition, sinomenine supplementation can suppress N-methyl-D-aspartate (NMDA) receptor-mediated Ca2+ influx and induce γ-aminobutyric acid type A (GABAA) receptor-mediated Cl− influx, each of which contributes to the improvement of morphine dependence and sleep disturbance. In this review, we outline the pharmacological effects and possible mechanisms of sinomenine in CNS disorders to advance the development of sinomenine as a new drug for the treatment of CNS disorders.
Cell metabolomics study on the anticancer effects of Ophiopogon japonicus against lung cancer cells using UHPLC/Q-TOF-MS analysis
Authors: Liu Qiao , Shen Jia-Man , Hong Hui-Jie , Yang Qi , Liu Wen , Guan Zhong , Wang Yi-Tao , Chen Xiao-Jia
Published: September 2022

Ophiopogon japonicus (OJ) is a traditional Chinese herbal medicine that has been used for thousands of years. Recently, the anticancer effects of OJ have been reported in multiple types of cancer, particularly in lung cancer. However, the underlying mechanisms remain unclear. In present study, the effects of OJ against NCI-H1299 human lung cancer cells were investigated, and the underlying mechanisms were explored using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS)-based cell metabolomics. As a result, OJ inhibited the proliferation, induced the apoptosis and suppressed the migration of NCI-H1299 cells. A total of 22 differential metabolites responsible for the effects of OJ were screened and annotated based on the LC-MS-based cell metabolomics approach. The altered metabolites were involved in three metabolic pathways, including glycerophospholipid metabolism, ether lipid metabolism and glutathione metabolism. These results showed that cell metabolomics-based strategies are promising tools to discover the action mechanisms of OJ against lung cancer cells.
Biological activities of meroterpenoids isolated from different sources
Authors: Fuloria Neeraj Kumar , Raheja Radhika K. , Shah Kaushal H. , Oza Manisha J. , Kulkarni Yogesh A. , Subramaniyan Vetriselvan , Sekar Mahendran , Fuloria Shivkanya
Published: September 2022

Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.
Liang-Ge decoction ameliorates acute lung injury in septic model rats through reducing inflammatory response, oxidative stress, apoptosis, and modulating host metabolism
Authors: He Wenju , Xi Qiang , Cui Huantian , Zhang Pingping , Huang Rui , Wang Taihuan , Wang Dongqiang
Published: September 2022

Liang-Ge decoction (LG) has been used in the treatment of early stage of spesis and can ameliorate sepsis-associated lung injury. However, the mechanism of LG on sepsis-associated lung injury remains unknown. In this study, we established a rat model of sepsis-associated lung injury using the cecal ligation and puncture (CLP) method, and investigated the therapeutic effects of LG on lung injury in rats with sepsis. In addition, the anti-inflammatory, anti-oxidative and anti-apoptotic effects of LG on sepsis-associated lung injury model rats were evaluated. Besides, untargeted metabolomics was used to investigate the regulation of metabolites in rats with sepsis-associated lung injury after LG treatment. Our results showed that LG could decrease the wet/dry (W/D) ratio in lung and the total cell count and total protein concentration in bronchoalveolar lavage fluid (BALF) in septic model rats. Hematoxylin and eosin (HE) staining showed that LG reduced the infiltration of pro-inflammatory cells in lung. In addition, LG treatmment down-regulated the gene and protein expression of pro-inflammatory cytokins in lung tissue and BALF. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were increased and the level of methane dicarboxylic aldehyde (MDA) was decreased in lung tissue homogenate in septic model rats after LG treament. Moreover, the numbers of apoptotic cells in lung were reduced and the activity of lactic dehydrogenase (LDH) in BALF was decreased in septic model rats after LG treament. Untargeted metabolomics analysis showed that LG treatment affected the levels of 23 metabolites in lung in septic model rats such as citric acid, methionine, threonine, alpha-ketoglutaric acid, and inositol, these metabolites were associated with the glycine, serine and threonine metabolism, cysteine and methionine metabolism, inositol phosphate metabolism and citrate cycle (TCA cycle) pathways. In conclusion, our study demonstrated the therapeutic effetcts of LG on sepsis-associated lung injury model rats. Moreover, LG could inhibit the inflammatory response, oxidative stress, apoptosis and regulate metabolites related to glycine, serine and threonine metabolism, cysteine and methionine metabolism, inositol phosphate metabolism and TCA cycle in lung in sepsis-associated lung injury model rats.
Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer
Authors: Qi Yihang , Zhang Wenxiang , Jiang Ray , Xu Olivia , Kong Xiangyi , Zhang Lin , Fang Yi , Wang Jingping , Wang Jing
Published: September 2022

Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogeneous results. We conducted this meta-analysis to yield insights into the efficacy and safety of the combination of ICIs and CT for TNBC patients in both the adjuvant and neoadjuvant settings.

Method: EMBASE, PUBMED, Cochrane, and www.clinicaltrials.gov databases were searched to determine potential eligible studies from the inception to 20 May 2022. Published RCTs on PD-1/PD-L1 ICIs combined with CT for TNBC patients were included.

Result: This meta-analysis included six double-blind RCTs comprising 4,081 TNBC patients treated with PD-1 or PD-L1 ICIs plus CT or placebo plus CT. The combination strategy benefited a better pathologic complete response (pCR) by 29% (RR = 1.29; 95% CI: 1.17–1.41; I2 = 0%) and a better progression-free survival (PFS) (HR = 0.82; 95% CI: 0.74–0.90; I2 = 0%) in the neoadjuvant and the adjuvant settings, respectively, especially in PD-L1-positive population (HR = 0.71; 95% CI: 0.62–0.81; I2 = 13%). The safety profiles were generally tolerable in both settings but the combination treatment will increase the risk of severe adverse events in the adjuvant setting (RR = 1.33; 95% CI 1.08–1.62, I2 = 0%). Additionally, the combination will increase the risk of any-grade hypothyroidism, hyperthyroidism, pneumonia, and rash in the adjuvant setting, and the risk of any-grade hypothyroidism, hyperthyroidism, infusion-related reactions, and severe cutaneous reactions in the neoadjuvant setting.

Conclusion: This meta-analysis demonstrated a significant pCR benefit and confirms the PFS benefit with PD-1/PD-L1 ICIs plus CT in TNBC patients with tolerable safety events in both neoadjuvant and adjuvant settings.