EXCLI Journal最新文献

This case report presents a comprehensive assessment and therapeutic intervention using non-invasive motor cortex neuromodulation for a 70-year-old female patient diagnosed with corticobasal degeneration (CBD). The study followed the CARE guidelines. The patient meets the criteria for probable CBD, with neuroimaging evidence of exclusively cortical impairment. The patient underwent a non-invasive neuromodulation protocol involving transcranial direct current stimulation (tDCS) and action observation plus motor imagery (AO+MI). The neuromodulation protocol comprised 20 sessions involving tDCS over the primary motor cortex and combined AO+MI. Anodal tDCS was delivered a 2 mA excitatory current for 20 minutes. AO+MI focused on lower limb movements, progressing over four weeks with video observation and gradual execution, both weekly and monthly. The neuromodulation techniques were delivered online (i.e. applied simultaneously in each session). Outcome measures were obtained at baseline, post-intervention and follow-up (1 month later), and included motor (lower limb), cognitive/neuropsychological and functional assessments. Walking speed improvements were not observed, but balance (Berg Balance Scale) and functional strength (Five Times Sit-to-Stand Test) improved post-treatment. Long-term enhancements in attentional set-shifting, inhibitory control, verbal attentional span, and working memory were found. There was neurophysiological evidence of diminished intracortical inhibition. Functional changes included worsening in Cortico Basal Ganglia Functional Scale score. Emotional well-being and general health (SF-36) increased immediately after treatment but were not sustained, while Falls Efficacy Scale International showed only long-term improvement. The findings suggest potential benefits of the presented neuromodulation protocol for CBD patients, highlighting multifaceted outcomes in motor, cognitive, and functional domains.

Malaria has developed as a serious worldwide health issue as a result of the introduction of resistant Plasmodium species strains. Because of the common chemo resistance to most of the existing drugs on the market, it poses a severe health problem and significant obstacles in drug research. Malaria treatment has evolved during the last two decades in response to Plasmodium falciparum drug sensitivity and a return of the disease in tropical areas. Plasmodium falciparum is now highly resistant to the majority of antimalarial drugs. The parasite resistance drew focus to developing novel antimalarials to combat parasite resistance. The requirement for many novel antimalarial drugs in the future year necessitates adopting various drug development methodologies. Different innovative strategies for discovering antimalarial drugs are now being examined here. This review is primarily concerned with the description of newly synthesized antimalarial compounds, i.e. Tafenoquine, Cipargamin, Ferroquine, Artefenomel, DSM265, MMV390048 designed to improve the activity of pure antimalarial enantiomers. In this review, we selected the representative malarial drugs in clinical trials, classified them with detailed targets according to their action, discussed the relationship within the human trials, and generated a summative discussion with prospective expectations.

Transglutaminase finds broad applications in the food industry, influencing texture, shelf life and overall food quality. It can be utilized to create products with enhanced sensory and technological properties and serves as a tool to reduce food waste. The aim of this study was to optimize the production of microbial transglutaminase (MTG) by the genetically unmodified strain of Streptoverticillium cinnamoneum KKP 1658. Tryptone soy broth (TSB) was chosen as the optimal inoculation medium due to its high MTG activity in the cultivation substrate. The optimal inoculum incubation time was determined as 24 hours, with a dosage of 10 %. Various nitrogen sources were investigated while maintaining a consistent nitrogen dosage (0.2 %) (including aminobak, corn steep liquor, ammonium nitrate and ammonium sulphate) to achieve the highest microbiological transglutaminase activity. The combination of aminobak with corn steep liquor and a cultivation period of 72 hours (28 °C; pH 6.0-6.5) yielded the highest MTG activity at 6.59 U/mL.

Given that tumor cells primarily instigate systemic changes through exosome secretion, our study delved into the role of colorectal cancer (CRC)-secreted exosomal miR-224 in stromal reprogramming and its impact on endothelial cell angiogenesis. Furthermore, we assessed the potential clinical significance of a specific signature of circulating serum-derived miRNAs, serving as a non-invasive biomarker for CRC diagnosis. Circulating serum-derived miR-103a-3p, miR-135b-5p, miR-182-5p, and miR-224-5p were significantly up-regulated, while miR-215-5p, and miR-455-5p showed a significant down-regulation in CRC patients than in healthy individuals. Our findings indicated that the expressions of CAF-specific markers (α-SMA and FAP) and CAF-derived cytokines (IL-6, and SDF-1) were induced in fibroblasts stimulated with SW480 CRC exosomes, partly due to Akt activation. As a plausible mechanism, exosomal transfer of miR-224 from SW40 CRC cells may activate stromal fibroblasts, which in turn, may promote endothelial cell sprouting. The study identified PHLPP1 and PHLPP2 as direct targets of miR-224 and demonstrated that CRC-secreted exosomal miR-224 activates Akt signaling by regulating PHLPP1/2 in activated fibroblasts, thereby affecting the stromal cell proliferation and migration. This study established a panel of six-circulating serum-derived miRNAs as a non-invasive biomarker for CRC diagnosis. Also, we proposed a supporting model in which CRC-secreted exosomal miR-224 takes part in the stromal reprogramming to CAFs partly through regulating Akt signaling. This may affect the malignant biological behavior of activated stromal cells and thereby elicit a vascular response within the microenvironment of CRC cells. See also the graphical abstract(Fig. 1).

Commonly used to decode the human brain's structural complexity, ex vivo dissection focuses on a given structure or region but cannot depict the whole brain organization (for example, its arterial distribution territories). Where dissection reaches its limit, the combination of tissue sectioning and 3D reconstruction may provide a volume for the assessment of structures from any view angle, following them dynamically to understand their spatial relationships. However, to produce sections, standard histological tissue processing protocols for paraffin embedding cannot be applied to a cerebral hemisphere as the latter is extensively larger than the conventional specimens. This paper presents a protocol for paraffin embedding of the whole human cerebral hemisphere and a method to reconstruct 3D volumes from serially sectioned and photographed paraffin blocks containing embedded hemispheres. Seven ex vivo whole human cerebral hemispheres were included, two were serially sectioned. Main cerebral arteries were injected with colored media to label arterial territories. A detailed description of every step, from tissue processing to image acquisition of cut blockfaces and volume reconstruction, is provided. Tissue processing and section cutting were reproducible, and the former provided complete and homogeneous paraffin wax impregnation. 3D visualization of the reconstructed whole human cerebral hemisphere successfully showed the distribution territories of the main cerebral arteries. In addition, we discuss the challenges we faced and overcame while developing the presented method and highlight its originality.

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P<0.1). Also, inflammatory factors in the enalapril group showed a decrease compared to the atrophy group. The strength of four limbs in the mice of the treatment group (-18.36 ± 1.70 %) was significantly higher than that of the atrophy group (-30.33 ± 3 %) at the end of the atrophy phase and also after 10 days of recovery. The results suggest that the use of enalapril that reduces the activation of angiotensin II-dependent pro-oxidant and pro-inflammatory pathways may improve the functional disorder and muscle necrosis in the murine model of muscle atrophy.