Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

Clinical predictors of surgical intervention for gastrointestinal magnetic foreign bodies in children.

BACKGROUND/AIMS: To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract. MATERIALS AND METHODS: From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study. RESULTS: In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P < 0.01). Logistic regression analysis showed that intermittent abdominal pain and abdominal muscle tension were independent risk factors for surgical treatment. CONCLUSION: Magnetic foreign bodies seriously endanger children's health. This study offers a single-center basis for the choice of surgical opportunity for intestinal obstruction or perforation caused by magnetic foreign bodies. Clinicians need immediate surgical intervention if the child shows symptoms of abdominal pain or abdominal tension.

Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease-related pathology via autophagy induction.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored. AIMS: This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action. MATERIALS & METHODS: Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aß- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed. RESULTS: The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aß- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aß and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine). DISCUSSION: LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE. CONCLUSION: Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.

The Application of Biomaterials in Spinal Cord Injury.

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.

The Protective Effects of Reineckia carnea Ether Fraction against Alzheimer's Disease Pathology: An Exploration in Caenorhabditis elegans Models.

Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aß(1-42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aß and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF's benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.

Targeting autophagy regulation in NLRP3 inflammasome-mediated lung inflammation in COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlight the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19.

Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota.

With the increase in human lifespan, population aging is one of the major problems worldwide. Aging is an irreversible progressive process that affects humans via multiple factors including genetic, immunity, cellular oxidation and inflammation. Progressive neuroinflammation contributes to aging, cognitive malfunction, and neurodegenerative diseases. However, precise mechanisms or drugs targeting age-related neuroinflammation and cognitive impairment remain un-elucidated. Traditional herbal plants have been prescribed in many Asian countries for anti-aging and the modulation of aging-related symptoms. In general, herbal plants' efficacy is attributed to their safety and polypharmacological potency via the systemic manipulation of the body system. Radix polygalae (RP) is a herbal plant prescribed for anti-aging and the relief of age-related symptoms; however, its active components and biological functions remained un-elucidated. In this study, an active methanol fraction of RP containing 17 RP saponins (RPS), was identified. RPS attenuates the elevated C3 complement protein in aged mice to a level comparable to the young control mice. The active RPS also restates the aging gut microbiota by enhancing beneficial bacteria and suppressing harmful bacteria. In addition, RPS treatment improve spatial reference memory in aged mice, with the attenuation of multiple molecular markers related to neuroinflammation and aging. Finally, the RPS improves the behavior and extends the lifespan of C. elegans, confirming the herbal plant's anti-aging ability. In conclusion, through the mouse and C. elegas models, we have identified the beneficial RPS that can modulate the aging process, gut microbiota diversity and rectify several aging-related phenotypes.

Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.

Tectochrysin increases stress resistance and extends the lifespan of Caenorhabditis elegans via FOXO/DAF-16.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Tectochrysin is a flavonoid compound and rich in a traditional Chinese Medicine Alpinia oxyphylla Miq., which has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, anti-diarrhea, hepatoprotective, and neuro-protective effects. Therefore, we tested if tectochrysin had an effect on aging in Caenorhabditis elegans (C. elegans). Our results showed that tectochrysin could extend the lifespan of C. elegans by up to 21.0%, delay the age-related decline of body movement, improve high temperature-stress resistance and anti-infection capacity, and protected worms against Aß1-42-induced toxicity. Tectochrysin could not extend the lifespan of the mutants from genes daf-2, daf-16, eat-2, aak-2, skn-1, and hsf-1. Tectochrysin could increase the expression of DAF-16 regulated genes. The extension of lifespan by tectochrysin requires FOXO/DAF-16 and HSF-1. Overall, our findings suggest that tectochrysin may have a potential effect on extending lifespan and age-related diseases.

Aspirin Derivative 5-(Bis(3-methylbut-2-enyl)amino)-2-hydroxybenzoic Acid Improves Thermotolerance via Stress Response Proteins in Caenorhabditis elegans.

Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity.

The function of the three phosphoribosyl pyrophosphate synthetase (Prs) genes in hyphal growth and conidiation in Aspergillus nidulans.

Phosphoribosyl pyrophosphate synthetase, which is encoded by the Prs gene, catalyses the reaction of ribose-5-phosphate and adenine ribonucleotide triphosphate (ATP) and has central importance in cellular metabolism. However, knowledge about how Prs family members function and contribute to total 5-phosphoribosyl-α-1-pyrophosphate (PRPP) synthetase activity is limited. In this study, we identified that the filamentous fungus Aspergillus nidulans genome contains three PRPP synthase-homologous genes (AnprsA, AnprsB and AnprsC), among which AnprsB and AnprsC but not AnprsA are auxotrophic genes. Transcriptional expression profiles revealed that the mRNA levels of AnprsA, AnprsB and AnprsC are dynamic during germination, hyphal growth and sporulation and that they all showed abundant expression during the vigorous hyphal growth time point. Inhibiting the expression of AnprsB or AnprsC in conditional strains produced more effects on the total PRPP synthetase activity than did inhibiting AnprsA, thus indicating that different AnPrs proteins are unequal in their contributions to Prs enzyme activity. In addition, the constitutive overexpression of AnprsA or AnprsC could significantly rescue the defective phenotype of the AnprsB-absent strain, suggesting that the function of AnprsB is not a specific consequence of this auxotrophic gene but instead comes from the contribution of Prs proteins to PRPP synthetase activity.

A prospective randomized trial comparing anterior cervical discectomy and fusion versus plate-only open-door laminoplasty for the treatment of spinal stenosis in degenerative diseases.

OBJECTIVE: For three or more involved cervical levels, there is a debate over which approach yields the best outcomes for the treatment of multilevel cervical degenerative disease. Our objective is to compare the radiological and clinical outcomes of two treatments for multilevel cervical degenerative disease: anterior cervical discectomy and fusion (ACDF) versus plate-only open-door laminoplasty (laminoplasty). METHODS: Patients were randomized on a 1:1 randomization schedule with 17 patients in the ACDF group and 17 patients in the laminoplasty group. Clinical outcomes were assessed by a visual analog scale (VAS), Japanese Orthopedic Association (JOA) scores, operative time, blood loss, rates of complications, drainage volume, discharge days after surgery, and complications. The cervical spine curvature index (CI) and range of motion (ROM) were assessed with radiographs. RESULTS: The mean VAS score, the mean JOA score, and the rate of complications did not differ significantly between groups. The laminoplasty group had greater blood loss, a longer operative time, more drainage volume, and a longer hospital stay than the ACDF group. There were no significant differences in the CI and ROM between the two groups at baseline and at each follow-up time point. ROM in both groups decreased significantly after surgery. CONCLUSIONS: Both ACDF and laminoplasty are effective and safe treatments for multilevel cervical degenerative disease. ACDF causes fewer traumas than laminoplasty.

Single-Level Rigid Fixation Combined with Coflex: A Biomechanical Study.

BACKGROUND: The purpose of this biomechanical in vitro study was to compare the kinematics and intradiscal pressure achieved with 2 methods: L4-L5 pedicle screw-rod fixation (PSRF) with an upper L3-L4 Coflex device and L4-L5 PSRF alone. The results were used to characterize the biomechanics of the topping-off operation with a Coflex device for the lumbar motion segment adjacent to single-level rigid fixation. MATERIAL/METHODS: Six human cadaveric spine specimens were biomechanically tested in vitro (6 males, 0 females). The 3-dimensional specimen motion in response to applied loads during flexibility tests was determined. Loads were applied along anatomic axes to induce flexion-extension, lateral bending, and axial rotation. All specimens were first studied with intact lumbar motion segments, then with L4-L5 PSRF alone, and finally with L4-L5 PSRF with an upper L3-L4 Coflex device. A non-paired comparison of the 3 configurations under 3 different conditions was made. RESULTS: PSRF, with or without a Coflex device, significantly increased the range of motion (ROM) in the upper adjacent motion segments in all directions of loading. The intradiscal pressure (IDP) changed slightly. A correlation analysis showed that the ROM and IDP are significantly positively correlated. The application of the upper motion segment of the Coflex device provided greater stability in all directions of motion than did PSRF alone, particularly for extension (p<0.05), while use of a Coflex device did not significantly decrease the IDP compared with PSRF alone (p>0.05). CONCLUSIONS: These results suggest that L4-L5 PSRF with an L3-L4 Coflex device is more stable than L4-L5 PSRF alone. PSRF with an upper Coflex device is a promising alternative to PSRF alone. Based on these biomechanical tests, it might be considered a protective method to prevent adjacent segment degeneration (ASD), although some limitations with this in vitro study must be addressed in the future.

Recurrent adamantinoma in the thoracolumbar spine successfully treated by three-level total en bloc spondylectomy by a single posterior approach.

PURPOSE: Adamantinoma is a low-grade primary malignant bone tumour with slow growth and local recurrence. Its occurrence in the spine is extremely rare, particularly with multilevel involvement. This paper wants to present the first case involving a patient with recurrent thoracolumbar spinal adamantinoma, who underwent a successful three-level spondylectomy for en bloc resection. METHODS: A 24-year-old man with osteolytic masses of T11 and T12 vertebral bodies was performed curettage by a posterior approach in 2008. The pathology report showed the excised neoplasm was a rare adamantinoma. This patient underwent a tumorectomy again because of its local recurrence nearly 3 years later. In 2012, it was unfortunately revealed that the excised tumour had relapsed and had spread to the L1 vertebral body. Due to its repeated recurrence and aggressive lesion, total en bloc spondylectomy (TES) for this malignant tumour was thought to be the best option for preventing repeated recurrence and possible cure. TES for T11-L1 thoracolumbar spine was performed and spinal reconstruction was completed with instrumentation and a titanium mesh cage through a one-stage single posterior approach. RESULTS: After three-level TES, neurological deficits of the patient demonstrated good recovery and no evidence of adamantinoma recurrence or deformity was found at 2-year follow-up. CONCLUSIONS: This is the first case involving multilevel thoracolumbar spinal adamantinoma with repeated recurrence to be successfully treated by three-level TES by a single posterior approach.

Surgical treatment for spinal tuberculosis with bilateral paraspinal abscess or bilateral psoas abscess: one-stage surgery.

STUDY DESIGN: This was a prospective study on the clinical outcomes of single-stage surgery for thoracic and lumbar spine tuberculosis patients with bilateral paraspinal or bilateral psoas abscesses. OBJECTIVE: The aim of this study was to investigate the feasibility of, indications for, and clinical effects of single-stage posterior surgery for the treatment of thoracic and lumbar spinal tuberculosis with bilateral paraspinal or bilateral psoas abscesses. SUMMARY OF BACKGROUND DATA: An increasing number of articles have been published on the use of single-stage surgery for spinal tuberculosis; however, none of these articles have discussed the use of such surgery in patients with bilateral abscesses. METHODS: Between January 2003 and January 2011, 41 patients with thoracic and lumbar spinal tuberculosis and bilateral paraspinal or bilateral psoas abscesses were treated with single-stage posterior surgery. All of the patients were treated preoperatively with 1-2 weeks of antituberculosis drugs. All patients were managed postoperatively with standard courses of chemotherapy with triple or quadruple antituberculosis drugs. The clinical symptoms, complications, and laboratory and image indicators were recorded. RESULTS: There were no local recurrences except in one L3-L4 tuberculosis patient. Two patients presented with extraspinal tuberculosis in the third year. There were no incision complications. Bone fusion was observed 6 months after the operation. The erythrocyte sedimentation rate was normal at 3 weeks-3 months postoperatively. There were no internal fixation failures. The internal fixations in 6 young patients were removed after the spinal tuberculosis was cured. CONCLUSIONS: Single-stage posterior surgery with instrumentation results in less operative trauma and can be a suitable alternative for treating thoracic and lumbar tuberculosis with bilateral paraspinal or bilateral psoas abscesses.

Molecular actions of ovarian cancer G protein-coupled receptor 1 caused by extracellular acidification in bone.

Extracellular acidification occurs under physiologic and pathologic conditions, such as exercise, ischemia, and inflammation. It has been shown that acidosis has various adverse effects on bone. In recent years there has been increasing evidence which indicates that ovarian cancer G protein-coupled receptor 1 (OGR1) is a pH-sensing receptor and mediates a variety of extracellular acidification-induced actions on bone cells and other cell types. Recent studies have shown that OGR1 is involved in the regulation of osteoclast differentiation, survival, and function, as well as osteoblast differentiation and bone formation. Moreover, OGR1 also regulates acid-induced apoptosis of endplate chondrocytes in intervertebral discs. These observations demonstrate the importance of OGR1 in skeletal development and metabolism. Here, we provide an overview of OGR1 regulation ofosteoclasts, osteoblasts, and chondrocytes, and the molecular actions of OGR1 induced by extracellular acidification in the maintenance of bone health.

Changes of peripheral blood α-L-fucosidase activity in patients with rheumatoid arthritis: a cross-sectional study.

Background: Rheumatoid arthritis (RA), a systemic autoimmune disease with approximately 1% prevalent population worldwide, which the etiology is still unclear. RA cannot be completely cured at present, which seriously affects the quality of life of patients. This study is to compare the peripheral blood α-L-fucosidase (AFU) between RA and healthy persons. Methods: A cross-sectional study was performed using total of 96 patients with RA served as case group and another 94 age-matched healthy volunteers served as a control group. AFU assay is detected by continuous monitoring method using Toshiba TBA-120FR (Tokyo, Japan) fully automatic biochemical analyzer in Japan, and the reagent is purchased from Zhejiang Quark Biological Company (Zhejiang, China). Statistical analysis was performed using SPSS 24.0 (SPSS, Inc., Chicago, IL, USA). Results: AFU activity in peripheral blood of RA patients were lower than healthy controls. The higher AFU activity, the shorter the course of disease (r=-0.2790, P=0.0065). The activity of lactate dehydrogenase in patients with RA is higher than that of healthy control, but the activity of acetylcholinesterase is lower than that of normal people. Finally, AFU activity was negatively correlated with the activity of lactate dehydrogenase (r=-0.2381, P=0.0208) and positively correlated with the activity of acetylcholinesterase (r=0.2985, P=0.0035). Conclusions: Changes of peripheral blood AFU activity might be associated with progression of disease in RA patients. The changes of AFU activity may lead to disturbances in glucose and lipid metabolism.

Exploring the therapeutic potential of Nelumbo nucifera leaf extract against amyloid-beta-induced toxicity in the Caenorhabditis elegans model of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) represents a critical global health challenge with limited therapeutic options, prompting the exploration of alternative strategies. A key pathology in AD involves amyloid beta (Aß) aggregation, and targeting both Aß aggregation and oxidative stress is crucial for effective intervention. Natural compounds from medicinal and food sources have emerged as potential preventive and therapeutic agents, with Nelumbo nucifera leaf extract (NLE) showing promising properties. Methods: In this study, we utilized transgenic Caenorhabditis elegans (C. elegans) models to investigate the potential of NLE in countering AD and to elucidate the underlying mechanisms. Various assays were employed to assess paralysis rates, food-searching capabilities, Aß aggregate accumulation, oxidative stress, lifespan under stress conditions, and the expression of stress-resistance-related proteins. Additionally, autophagy induction was evaluated by measuring P62 levels and the formation of LGG-1+ structures, with RNAi-mediated inhibition of autophagy-related genes to confirm the mechanisms involved. Results: The results demonstrated that NLE significantly reduced paralysis rates in CL4176 and CL2006 worms while enhancing food-searching capabilities in CL2355 worms. NLE also attenuated Aß aggregate accumulation and mitigated Aß-induced oxidative stress in C. elegans. Furthermore, NLE extended the lifespan of worms under oxidative and thermal stress conditions, while concurrently increasing the expression of stress-resistance-related proteins, including SOD-3, GST-4, HSP-4, and HSP-6. Moreover, NLE induced autophagy in C. elegans, as evidenced by reduced P62 levels in BC12921 worms and the formation of LGG-1+ structures in DA2123 worms. The RNAi-mediated inhibition of autophagy-related genes, such as bec-1 and vps-34, negated the protective effects of NLE against Aß-induced paralysis and aggregate accumulation. Discussion: These findings suggest that NLE ameliorates Aß-induced toxicity by activating autophagy in C. elegans. The study underscores the potential of NLE as a promising candidate for further investigation in AD management, offering multifaceted approaches to mitigate AD-related pathology and stress-related challenges.

Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease-modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD. METHODS: The neuroprotective effect of CFE in H2O2- or 6-OHDA-induced PC-12 cells and α-synuclein-overexpressing PC-12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α-synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α-synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging-related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria. RESULTS: In cellular models of PD, CFE significantly attenuated H2O2- or 6-OHDA-induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α-synuclein in wide type (WT)-, A53T-, A30P-, or E46K-α-synuclein-overexpressing PC-12 cells. Our further findings reveal that CFE administration reduced α-synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6-OHDA-induced degeneration in BZ555 worms, extended lifespan, delayed aging-related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo. CONCLUSION: Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.