This study was to examine the kinematics, muscle activities, and perceived physical exertion in different regions of the spine during patient transfers by nursing students between a bed and a ...wheelchair, with or without a transfer belt in a laboratory setting. Results showed that with the effect of the belt, the % maximum voluntary contraction of the lumbar erector spinae was reduced significantly by nearly 10%. Muscle activity was significantly increased in thoracic erector and multifidus spinae during wheelchair-to-bed transfer, compared to bed-to-wheelchair transfers. There was no significant effect of belt or task on the spinal angular displacement in different spinal regions. Using the transfer belt was associated with a significantly decreased score for perceived exertion. In conclusion, this study supports the use of a transfer belt contributing to lower muscle activity and lower perceived physical exertion in the low back.
•Transfer belts can reduce muscle activity and perceived physical exertion in the low back region.•Proper posture and correct techniques in patient transfers are key elements in reducing the risk of low back disorders.•Low-tech patient transfer assistive devices can be used to reduce the risk of low back disorders.
We published a study showing that improvement in response to splenectomy associated defective, in regards to the antibody response to Pneumovax
23 (23-valent polysaccharides, PPSV23), can be achieved ...by splenocyte reinfusion. This study triggered a debate on whether and how primary and secondary immune responses occur based on humoral antibody responses to the initial vaccination and revaccination. The anti-SARS-CoV-2 vaccine sheds new light on the interpretation of our previous data. Here, we offer an opinion on the administration of the polyvalent polysaccharide vaccine (PPSV23), which appears to be highly relevant to the primary vaccine against SARS-CoV-2 and its booster dose. Thus, we do not insist this is a secondary immune response but an antibody response, nonetheless, as measured through IgG titers after revaccination. However, we contend that we are not sure if these lower but present IgG levels against pneumococcal antigens are clinically protective or are equally common in all groups because of the phenomenon of "hyporesponsiveness" seen after repeated polysaccharide vaccine challenge. We review the literature and propose a new mechanism-caveolae memory extracellular vesicles (CMEVs)-by which polysaccharides mediate prolonged and sustained immune response post-vaccination. We further delineate and explain the data sets to suggest that the dual targets on both Cav-1 and SARS-CoV-2 spike proteins may block the viral entrance and neutralize viral load, which minimizes the immune reaction against viral attacks and inflammatory responses. Thus, while presenting our immunological opinion, we answer queries and responses made by readers to our original statements published in our previous work and propose a hypothesis for all vaccination strategies, i.e., caveolae-mediated extracellular vesicle-mediated vaccine memory.
In the bone marrow microenvironment (BMME), mesenchymal stem/stromal cells (MSCs) control the self-renewal of both healthy and cancerous hematopoietic stem/progenitor cells (HSPCs). We previously ...showed that
leukemia-derived MSCs change neighbor MSCs into leukemia-permissive states and boost leukemia cell proliferation, survival, and chemotherapy resistance. But the mechanisms behind how the state changes are still not fully understood.
Here, we took a reverse engineering approach to determine BCR-ABL1+ leukemia cells activated transcriptional factor C/EBPβ, resulting in miR130a/b-3p production. Then, we back-tracked from clinical specimen transcriptome sequencing to cell co-culture, molecular and cellular assays, flow cytometry, single-cell transcriptome, and transcriptional regulation to determine the molecular mechanisms of BCR-ABL1-driven exosome-miR130b-3p-mediated gap-junction Cx43 MSC intercellular communications.
BCR-ABL1-driven exosome-miR130a/b-3p mediated gap-junction Cx43 (a.k.a., GJA1) BMSC intercellular communications for subclonal evolution in leukemic microenvironment by targeting BMSCs-expressed HLAs, thereby potentially maintaining BMSCs with self-renewal properties and reduced BMSC immunogenicity. The Cx43
and miR-130a/b
subclonal MSCs subsets of differentiation state could be reversed to Cx43
and miR-130a/b
subclones of the higher stemness state in Cx43-overexpressed subclonal MSCs. Both miR-130a and miR-130b might only inhibit Cx43 translation or degrade Cx43 proteins and did not affect Cx43 mRNA stability. The subclonal evolution was further confirmed by single-cell transcriptome profiling of MSCs, which suggested that Cx43 regulated their stemness and played normal roles in immunomodulation antigen processing. Thus, upregulated miR-130a/b promoted osteogenesis and adipogenesis from BMSCs, thereby decreasing cancer progression. Our clinical data validated that the expression of many genes in human major histocompatibility was negatively associated with the stemness of MSCs, and several immune checkpoint proteins contributing to immune escape in tumors were overexpressed after either miR-130a or miR-130b overexpression, such as CD274, LAG3, PDCD1, and TNFRSF4. Not only did immune response-related cytokine-cytokine receptor interactions and PI3K-AKT pathways, including EGR3, TNFRSF1B, but also NDRG2 leukemic-associated inflammatory factors, such as IFNB1, CXCL1, CXCL10, and CCL7 manifest upon miR-130a/b overexpression. Either BCR siRNAs or ABL1 siRNAs assay showed significantly decreased miR-130a and miR-130b expression, and chromatin immunoprecipitation sequencing confirmed that the regulation of miR-130a and miR-130b expression is BCR-ABL1-dependent. BCR-ABL1 induces miR-130a/b expression through the upregulation of transcriptional factor C/EBPβ. C/EBPβ could bind directly to the promoter region of miR-130b-3p, not miR-130a-3p. BCR-ABL1-driven exosome-miR130a-3p could interact with Cx43, and further impact GJIC in TME.
Our findings shed light on how leukemia BCR-ABL1-driven exosome-miR130b-3p could interact with gap-junction Cx43, and further impact GJIC in TME, implications for leukemic therapies of subclonal evolution.
Bone marrow mesenchymal stem cells (BMSCs), the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches ...for hematopoietic stem cells (HSCs). However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy. Moreover, the differentiation balance of BMSCs is crucial to hematopoiesis. We highlight the negative effects of differentiation bias of BMSCs on hematopoietic recovery after bone marrow transplantation. Keeping the differentiation balance of BMSCs is critical for hematopoietic recovery. This review summarises current understanding about how BMSC differentiation affects hematopoiesis and its potential application in improving hematopoietic recovery after bone marrow transplantation.
Developing ecological approaches for disease control is critical for future sustainable aquaculture development. White spot syndrome (WSS), caused by white spot syndrome virus (WSSV), is the most ...severe disease in cultured shrimp production. Culturing specific pathogen-free (SPF) broodstock is an effective and widely used strategy for controlling WSS. However, most small-scale farmers, who predominate shrimp aquaculture in developing countries, cannot cultivate SPF shrimp, as they do not have the required infrastructure and skills. Thus, these producers are more vulnerable to WSS outbreaks than industrial farms. Here we developed a shrimp polyculture system that prevents WSS outbreaks by introducing specific fish species. The system is easy to implement and requires no special biosecurity measures. The promotion of this system in China demonstrated that it allowed small-scale farmers to improve their livelihood through shrimp cultivation by controlling WSS outbreaks and increasing the production of ponds.
Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the ...original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner.
Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a "watchand- wait" approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology - a balance that needs to be maintained for the "watch-and-wait" approach to cancer.
This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.
Qigong is a meditative movement with therapeutic effects and is commonly practiced in Eastern medicine. A growing body of evidence validates its health benefits, leading to mechanistic questions ...about how it works. We propose a novel mechanism by which the "acid" caused by hypoxia affects metabolism, and the way it is neutralized through Qigong practice involves the body's blood flow and vasculature modifications. Specifically, Qigong exercise generates an oxygen supply and acid-base balance against the hypoxic effects of underlying pathological conditions. We also propose that Qigong exercise mediated and focused on the local hypoxia environment of tissues might normalize the circulation of metabolic and inflammation accumulation in the tumor tissue and restore the normal metabolism of tissues and cells through calm, relaxation, and extreme Zen-style breathing that gravitates toward preemptive health and medicine. Thus, we propose the mechanisms of action related to Qigong, intending to unify Eastern and Western exercise theory.
Half of the population of non-small cell lung cancer (NSCLC) patients are older than 70 years and have limited therapeutic options due to poor tolerance and being excluded in most clinical trials. ...Anlotinib hydrochloride, a novel oral multi-target tyrosine kinase inhibitor, has been approved for the standard third-line treatment for NSCLC in China. Herein we report an elderly NSCLC patient without any driver gene mutations who was undergoing anlotinib as a front-line treatment and who achieved long-term survival.
The 77-year-old male patient was admitted to the hospital for chest tightness after engaging in physical activity for a week. The patient has been diagnosed with stage IIIB driver gene-negative squamous cell lung carcinoma. After that, he was treated with anlotinib for 2 years and 10 months from the first diagnosis until the last disease progression. Briefly, anlotinib combined with platinum-based chemotherapy was performed as the first-line therapy over six cycles. After 6 more cycles of anlotinib monotherapy maintenance, disease progression occurred. Then, anlotinib combined with tegafur was administered as a salvage treatment, and the disease was controlled again. After 29 cycles of anlotinib combined with tegafur regimens, the disease progressed finally. The patient achieved a total of 34 months of progression-free survival after anlotinib was used as the front-line treatment. He is still alive with a good performance status now (performance status score: 1).
This patient achieved long-term survival using anlotinib as a front-line regimen combined with chemotherapy.
Introduction
Neuroblastoma (NB) is one of the children’s most common solid tumors, accounting for approximately 8% of pediatric malignancies and 15% of childhood cancer deaths. Somatic mutations in ...several genes, such as ALK, have been associated with NB progression and can facilitate the discovery of novel therapeutic strategies. However, the differential expression of mutated and wild-type alleles on the transcriptome level is poorly studied.
Methods
This study analyzed 219 whole-exome sequencing datasets with somatic mutations detected by MuTect from paired normal and tumor samples.
Results
We prioritized mutations in 8 candidate genes (RIMS4, RUSC2, ALK, MYCN, PTPN11, ALOX12B, ZNF44, and CNGB1) as potential driver mutations. We further confirmed the presence of allele-specific expression of the somatic mutations in NB with integrated analysis of 127 RNA-seq samples (of which 85 also had DNA-seq data available), including MYCN, ALK, and PTPN11. The allele-specific expression of mutations suggests that the same somatic mutation may have different effects on the clinical outcomes of tumors.
Conclusion
Our study suggests 2 novel variants of ZNF44 as a novel candidate driver gene for NB.
This study reports that single-cell molecular analysis overcomes problems associated with the heterogeneity of bulk tumors for monitoring tumor subclonal evolution and molecular pathways relevant to ...GBM relapse.
Abstract
Glioblastoma multiforme (GBM) remains an incurable brain tumor. The highly malignant behavior of GBM may, in part, be attributed to its intraclonal genetic and phenotypic diversity (subclonal evolution). Identifying the molecular pathways driving GBM relapse may provide novel, actionable targets for personalized diagnosis, characterization of prognosis and improvement of precision therapy. We screened single-cell transcriptomes, namely RNA-seq data of primary and relapsed GBM tumors from a patient, to define the molecular profile of relapse. Characterization of hundreds of individual tumor cells identified three mutated genes within single cells, involved in the RAS/GEF GTP-dependent signaling pathway. The identified molecular pathway was further verified by meta-analysis of RNA-seq data from more than 3000 patients. This study showed that single-cell molecular analysis overcomes the inherent heterogeneity of bulk tumors with respect to defining tumor subclonal evolution relevant to GBM relapse.
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