Advances in hematopoietic stem cell transplantation for autoimmune diseases.

Autoimmune diseases (ADs) are a collection of immunological disorders in which the immune system responds to self-antigens by producing autoantibodies or self-sensitized cells. Current treatments are unable to cure ADs, and achieving long-term drug-free remission remains a challenging task. Hematopoietic stem cell transplantation (HSCT) stands out from other therapies by specifically targeting ADs that target various cell subpopulations, demonstrating notable therapeutic benefits and resulting in sustained drug-free remission. Since different ADs have distinct mechanisms of action, the comprehensive understanding of how HSCT works in treating ADs is crucial. This review provides a detailed overview of the latest research and clinical applications of HSCT in treating ADs, offering new insights for clinicians aiming to optimize its use for ADs management.

Low-Dose Treatment with Epirubicin, a Novel Histone Deacetylase 1 Inhibitor, Exerts Anti-leukemic Effects by Inducing Ferroptosis.

AIMS: Leukemia is hematopoietic stem cell malignant tumor with poor outcomes. Histone deacetylase 1 (HDAC1) is highly expressed in leukemia and current HDAC1 inhibitors have clinical limitations in leukemia therapy. Therefore, novel HDAC1 inhibitor is imperative to being found and its mechanism needs to be further explored. MATERIALS AND METHODS: Novel HDAC1 inhibitors were discovered through drug virtual screening. CCK-8, EdU and soft agar assay were used to assess the anti-leukemic effect of the candidate HDAC1 inhibitor. ROS, lipid peroxidation, intracellular Fe2+ and LIP assay were employed to verify cell ferroptosis. Additionally, a xenograft model was performed to explore the efficacy and safety of candidate HDAC1 inhibitor in vivo. RESULTS: HDAC1 might be a promising therapeutic target for leukemia and Epirubicin (Epi) could be used as a potential HDAC1 inhibitor. Low-dose Epi exhibited good anti-leukemic effects by inhibiting cell proliferation, DNA synthesis and colony formation. Low-dose Epi could induce ferroptosis by triggering lipid peroxidation, which was better than that treated with current HDAC1 inhibitors Chidamide or Vorinostat, ROS generation and Fe2+ overload in leukemia cells. Mechanistically, low-dose Epi induced ferroptosis by targeting amino acid metabolism and iron metabolism. Similar results were found in a xenograft model in NOG mice with a good safety profile. CONCLUSION: Our study demonstrated that Epi might be used as a HDAC1 inhibitor. Low-dose Epi could inhibit tumor progression by inducing cell ferroptosis in vitro and in vivo. Thus, Epi administration with lower concentration may be much more favorable and safer in the treatment with leukemia.

Bulk/Interfacial Structure Design of Li-Rich Mn-Based Cathodes for All-Solid-State Lithium Batteries.

Li-rich Mn-based cathode materials (LRMO) are promising for enhancing energy density of all-solid-state batteries (ASSBs). Nonetheless, the development of efficient Li+/e- pathways is hindered by the poor electrical conductivity of LRMO cathodes and their incompatible interfaces with solid electrolytes (SEs). Herein, we propose a strategy of in-situ bulk/interfacial structure design to construct fast and stable Li+/e- pathways by introducing Li2WO4, which reduces the energy barrier for Li+ migration and enhances the stability of the surface oxygen structure. The reversibility of oxygen redox was improved, and the voltage decay of the LRMO cathode was addressed significantly. As a result, the bulk structure of the LRMO cathodes and the high-voltage solid-solid interfacial stability are improved. Therefore, the ASSBs achieve a high areal capacity (∼3.15 mAh/cm2) and outstanding cycle stability of ≥1200 cycles with 84.1% capacity retention at 1 C at 25 °C. This study offers new insights into LRMO cathode design strategies for ASSBs, focusing on ultrastable high-voltage interfaces and high-loading composite electrodes.

Drp1 Promotes Macrophage M1 Polarization and Inflammatory Response in Autoimmune Myocarditis by Driving Mitochondrial Fission.

Autoimmune myocarditis (AM) is characterized by an intricate inflammatory response within the myocardium. Dynamin-related protein 1 (Drp1), a pivotal modulator of mitochondrial fission, plays a role in the pathogenesis of various diseases. A myosin-induced experimental autoimmune myocarditis (EAM) mouse model was successfully established. Flow cytometry was employed to detect M1/M2-like macrophages. Mitochondrial fragmentation was assessed using Mito-Tracker Red CMXRos. Drp1 was upregulated and activated in EAM mice. Depletion of Drp1 was observed to mitigate inflammation, macrophage infiltration and M1 polarization within the cardiac tissue of EAM mice. In M1-like macrophages derived from the hearts of EAM mice, Drp1 was found to promote mitochondrial fission and diminish mitochondrial fusion. Furthermore, the depletion of Drp1 reduced the NF-κB-related pro-inflammatory response in EAM-associated M1-like macrophages. Drp1 drives mitochondrial fission in macrophages, driving their M1 polarization and the subsequent inflammatory response. Drp1 may represent an effective target for the prevention and treatment of AM.

Detection of tetracycline by molecularly imprinted electrochemical sensor based on the modification of poly(3,4-propylene dioxythiophene)/chitosan/au.

In this study, a molecularly imprinted polymer (MIP) electrochemical sensor based on poly(3,4-propylenedioxythiophene)/chitosan/Au (PProDOT/CS/Au) composite modification was designed for highly sensitive and selective detection of TC. Green synthesis of CS/Au without the use of reducing agents, followed by in-situ oxidation polymerization of PProDOT. The high electrochemical activity and high stability of PProDOT, the numerous functional groups (-OH, -NH2) of CS, and the excellent electron transport capacity of AuNPs, which provided a suitable incubation chamber for the production of imprinted cavities. Meanwhile, combined with the specific recognition ability of MIP, it showed superior performance over bare glassy carbon electrodes. Under the optimal experimental conditions, this sensor showed good linearity for TC in the concentration ranges of 0.0001-100 µM, with a low limit of detection (LOD) of 0.19 nM. At the same time, the sensor exhibited satisfactory selectivity, repeatability, reproducibility and stability. It was evident from the results of the study that the sensor designed in this paper showed considerable potential for application in the detection of TC in pharmaceuticals, the environment, and food samples.

Trajectories and Predictors of Weight-Bearing and Non-Weight-Bearing Pain in Knee Osteoarthritis: A 9-Year Follow-Up Study.

Objective: To identify distinct developmental trajectories of weight-bearing pain (WBP) and non-weight-bearing pain (NWBP) and examine the trajectory predictors in individuals with or at risk of knee osteoarthritis. Methods: We included 971 participants from the Osteoarthritis Initiative whose baseline magnetic resonance imaging data and 9-year follow-up data on pain were available. We applied group-based trajectory modeling to identify WBP and NWBP trajectories over 9 years. Univariate and multivariate multinomial logistic regression analyses were performed to examine the predictors of identified trajectories. Results: Three distinct WBP trajectories were identified: "no pain" (32.4%), "mild pain" (44.6%), and "moderate pain" (23%). Three distinct NWBP trajectories were identified: "no pain" (50.9%), "mild pain" (33.4%), and "moderate pain" (15.7%). In multivariate analyses, high body mass index, depression, multisite pain, radiographic knee OA, and comorbidities were associated with worse development trajectories for WBP and NWBP. Weak quadriceps strength and bone marrow lesion were only associated with worse WBP trajectories, whereas low education level was only associated with worse NWBP trajectories. Conclusion: The developmental course of pain is heterogeneous in WBP or NWBP. Quadriceps strength and bone marrow leisure may be WBP-specific predictors, whereas education level may be a NWBP-specific predictor. The assessment of knee pain should be more accurate, which may help select appropriate therapeutic targets.

Simulating Upper Eyelid Ptosis During Neuromodulator Injections-An Exploratory Injection and Dissection Study.

BACKGROUND: Aesthetic neuromodulator injections of the upper face are frequently performed to temporarily block muscular actions of the periorbital muscles to ultimately reduce skin rhytids. However, the adverse event rate in the literature for toxin-induced blepharoptosis ranges from 0.51% to 5.4%. OBJECTIVE: To identify access pathways by which injected neuromodulator product can travel from extra- to intra-orbital and therefore affect the levator palpebrae superioris muscle. METHODS: Nine non-embalmed human body donors were investigated in this study with a mean age at death of 72.8 (16.1) years. The 18 supraorbital regions were injected in 28 times (14 for supratrochlear and 14 for supraorbital) with 0.5 cc, whereas eight cases (four for supratrochlear and four supraorbital) were injected with 0.1 cc of colored product. Anatomic dissections were conducted to identify structures stained by the injected color. RESULTS: The results of this injection- and dissection-based study revealed that both the supratrochlear and the supraorbital neurovascular bundles are access pathways for injected neuromodulator products to reach the intra-orbital space and affect the levator palpebrea superioris muscle. Out of 36 conducted injection passes, seven (19.44%) resulted in affection of the sole elevator of the eyelid of which 100% occurred only at an injection volume of 0.5 cc and not at 0.1 cc. CONCLUSION: Clinically, the results indicate that a low injection volume, a superficial injection for the supraorbital location, and angling the needle tip away from the supratrochlear foramen (toward the contralateral temple) when targeting the corrugator supercilii muscles, can increase the safety profile of an aesthetic toxin glabellar treatment.

Biological aging mediates the association between volatile organic compounds and cardiovascular disease.

BACKGROUND: Evidence for the relationship between individual and combined volatile organic compounds (VOCs) and cardiovascular disease (CVD) is limited. Besides, the mediating role of biological aging (BA) has not been studied. Therefore, this study aimed to examine the association between VOCs and CVD risk and to explore the mediating effects of BA. METHODS: Logistic regression models were used to investigate the relationships of metabolites of volatile organic compounds (mVOCs) and BA with CVD. In addition, weighted quantile sum (WQS) regression, adaptive elastic networks, and Environmental Risk Score (AENET-ERS) were utilized to assess overall associations of mixed VOCs co-exposure with CVD. Mediation analyses were used to identify potential mediating effects of BA. RESULTS: In the single-pollutant model, CYMA was shown to be associated with an increased risk of CVD. Additionally, we identified significantly positive associations between the WQS index and CVD (odds ratio (OR) = 1.292, 95% confidence interval (CI): 1.006, 1.660), and DHBMA had the greatest contribution for CVD (0.246). Furthermore, the AENET-ERS results showed that 8 mVOCs were significantly associated with CVD, and ERS was related to an elevated risk of CVD (OR = 1.538, 95%CI: 1.255, 1.884). Three BA indicators mediated the association of the mVOCs mixture with CVD, with mediating effect proportions of 11.32%, 34.34%, and 7.92%, respectively. CONCLUSION: The risk of CVD was found to increase with both individual and combined exposure to VOCs. BA mediates the positive effects of VOCs on CVD, suggesting that this pathway may be one of the mechanisms of CVD.

[Clinical Features and Prognosis of Patients with Diffuse Large B-Cell Lymphoma of the Breast].

OBJECTIVE: To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast. METHODS: The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed. RESULTS: There were significant differences in IPI score, LDH level and ß2- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was （59.1±19.8）% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05). CONCLUSION: Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and ß2-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.

AP1c and SOC1 Form a Regulatory Feedback Loop to Regulate Flowering Time in Soybean.

Flowering time is a key agronomic trait that directly affects soybean yield. Both APETALA1 (AP1) and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) regulate flowering time in soybean, but their genetic and regulatory relationships have not been clarified. Here, we report that AP1c physically interacted with two SOC1 proteins, SOC1a and SOC1b, and that these SOC1s upregulated the expression of AP1c, promoting flowering. Moreover, AP1c repressed the expression of the SOC1s by directly binding to their promoters, thus preventing plants from flowering too early. These findings indicate that AP1c and SOC1s form a regulatory feedback loop that regulates flowering time. Importantly, we identified an exceptional allele, AP1cG, that was selected for during soybean domestication and promotes the early-flowering phenotype in cultivated soybean. Collectively, our work identifies a previously unknown allelic combination potentially useful for both classical and molecular soybean breeding.

Feasibility of augmented reality combine patient-specific implants (PSI) applied to navigation in mandibular genioplasty: A phantom experiment.

PURPOSE: Genitoplasty is becoming more and more common, and it is important to improve the accuracy of the procedure and simplify the procedure. This experiment explores the feasibility of using augmented reality (AR) technology combined with PSI titanium plates for navigational assistance in genioplasty performed on models, aiming to study the precision of such surgical interventions. METHODS: Twelve genioplasty procedures were designed and implemented on 3D-printed resin mandibular models by the same surgeon using three different approaches: AR+3DT group (AR+PSI) , 3DT group (patient-specific titanium plate) , and a traditional free-hand group(FH group). Postoperative models were assessed using CBCT to evaluate surgical accuracy. RESULTS: In terms of osteotomy accuracy, the AR group demonstrated a surgical error of 0.9440±0.5441 mm, significantly lower than the control group, which had an error of 1.685±0.8907 mm (P < 0.0001). In experiments positioning the distal segment of the chin, the overall centroid shift in the AR group was 0.3661±0.1360 mm, significantly less than the 2.304±0.9629 mm in the 3DT group and 1.562±0.9799 mm in the FH group (P < 0.0001). Regarding angular error, the AR+3DT group showed 2.825±1.373°, significantly <8.283±3.640° in the 3DT group and 7.234±5.241° in the FH group. CONCLUSION: AR navigation technology combined with PSI titanium plates demonstrates higher surgical accuracy compared to traditional methods and shows feasibility for use. Further validation through clinical trials is necessary.

Loss of SELENOW aggravates muscle loss with regulation of protein synthesis and the ubiquitin-proteasome system.

Sarcopenia is characterized by accelerated muscle mass and function loss, which burdens and challenges public health worldwide. Several studies indicated that selenium deficiency is associated with sarcopenia; however, the specific mechanism remains unclear. Here, we demonstrated that selenoprotein W (SELENOW) containing selenium in the form of selenocysteine functioned in sarcopenia. SELENOW expression is up-regulated in dexamethasone (DEX)-induced muscle atrophy and age-related sarcopenia mouse models. Knockout (KO) of SELENOW profoundly aggravated the process of muscle mass loss in the two mouse models. Mechanistically, SELENOW KO suppressed the RAC1-mTOR cascade by the interaction between SELENOW and RAC1 and induced the imbalance of protein synthesis and degradation. Consistently, overexpression of SELENOW in vivo and in vitro alleviated the muscle and myotube atrophy induced by DEX. SELENOW played a role in age-related sarcopenia and regulated the genes associated with aging. Together, our study uncovered the function of SELENOW in age-related sarcopenia and provides promising evidence for the prevention and treatment of sarcopenia.

Convective Water Vapour Energy Ablation (Rezum®) versus Prostatic Urethral Lift (Urolift®); A 2-Year Prospective Study.

Introduction To compare the clinical outcomes and complication rates of Convective Water Vapour Energy Ablation (Rezum®) and Prostatic Urethral Lift (Urolift®). To identify predictive factors for treatment failures in both treatments. Materials & Methods Prospective clinico-epidemiological data of patients who underwent Urolift® or Rezum® in a single institution for Benign Prostatic Hyperplasia (BPH) was collected. The choice of intervention depended on the preference of the patients after patient-centric discussions. Results From October 2019 to October 2022, 86 patients underwent Rezum® and 62 patients underwent Urolift®. Rezum® involved a longer indwelling catheter duration (12.38±5.548 versus 1.39±3.010 days, p<0.001) compared to Urolift®. Rezum® was associated with more complications compared to Urolift® (36 (41.9%) versus 10 (16.1%) cases, p<0.001). Rezum® had more cases of hematuria (17 (19.8%) versus 4 (6.5%) cases (p=0.022)) and urinary tract infections (27 (31.4%) versus 3 (4.8%) cases, p<0.001)), compared to Urolift®. There were no significant differences in Clavien-Dindo Grade 3-5 complications between the interventions. Urolift® was associated with higher re-operation rates (5 (8.1%) versus 0 (0%) cases, p=0.010) compared Rezum®. Rezum® had higher anti-cholinergic usage rates compared to Urolift® post-operation (22 (25.6%) versus 8 (12.9%) cases, p=0.024). Both interventions showed improvement in International Prostate Symptom Score (IPSS), Quality of Life score, and peak velocity flow over the 2 years with no significant difference between the two. Based on receiver operating characteristic curve, pre-operation IPSS ≥ 16 had 95.7% sensitivity and 38.4% specificity to predict the probability of treatment failures after the interventions. Conclusions There was no difference in clinical outcomes of patients who underwent Rezum® and Urolift®. However, patients who had undergone Rezum® faced more minor complications and more required anti-cholinergic medications. Lastly, physicians should note that patients with IPSS≥16 would unlikely benefit from either intervention.

Structure-inclusive similarity based directed GNN: a method that can control information flow to predict drug-target binding affinity.

MOTIVATION: Exploring the association between drugs and targets is essential for drug discovery and repurposing. Comparing with the traditional methods that regard the exploration as a binary classification task, predicting the drug-target binding affinity can provide more specific information. Many studies work based on the assumption that similar drugs may interact with the same target. These methods constructed a symmetric graph according to the undirected drug similarity or target similarity. Although these similarities can measure the difference between two molecules, it is unable to analyze the inclusion relationship of their substructure. For example, if drug A contains all the substructures of drug B, then in the message-passing mechanism of the graph neural network, drug A should acquire all the properties of drug B, while drug B should only obtain some of the properties of A. RESULTS: To this end, we proposed a structure-inclusive similarity (SIS) which measures the similarity of two drugs by considering the inclusion relationship of their substructures. Based on SIS, we constructed a drug graph and a target graph, respectively, and predicted the binding affinities between drugs and targets by a graph convolutional network-based model. Experimental results show that considering the inclusion relationship of the substructure of two molecules can effectively improve the accuracy of the prediction model. The performance of our SIS-based prediction method outperforms several state-of-the-art methods for drug-target binding affinity prediction. The case studies demonstrate that our model is a practical tool to predict the binding affinity between drugs and targets. AVAILABILITY AND IMPLEMENTATION: Source codes and data are available at https://github.com/HuangStomach/SISDTA.

A Cross-Sectional Survey of Fixed-Dose Combination Antihypertensive Medicine Prescribing in Twenty-Four Countries, Including Qualitative Insights.

Background: Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide. Methods: A cross-sectional survey was conducted online from June 2023 to January 2024 to recruit doctors. We collaborated with an international network of researchers and clinicians identified through institutional connections. A passive snowballing recruitment strategy was employed, where network members forwarded the survey link to their clinical colleagues. The survey instrument, developed through a literature review, interviews with academic and clinical researchers, and pilot testing, assessed participants perspectives on prescribing FDC antihypertensive medicines for hypertension. Participants rated their level of agreement (5-point Likert scale) with statements representing six barriers and four facilitators to FDC use. Findings: Data from 191 surveys were available for analysis. 25% (n = 47) of participants worked in high-income countries, 38% (n = 73) in upper-middle income, 25% (n = 48) in lower-middle income, 6% (n = 10) in low-income countries. Forty percent (n = 70) of participants were between 36-45 years of age; two thirds were male. Cost was reported as a barrier to prescribing FDC antihypertensive medicines [51% (n = 87) agreeing or strongly agreeing], followed by doctors' confidence in BP measured in clinic [40%, (n = 70)], access [37%, (n = 67)], appointment duration [35%, (n = 61)], concerns about side-effects [(21%, n = 37)], and non-adherence [12%, (n = 21)]. Facilitators to FDC antihypertensive polypills prescribing were clinician facing, such as access to educational supports [79%, (n = 143)], more BP measurement data [67%, (n = 120)], a clinical nudge in health records [61%, (n = 109)] and patient-facing including improved patient health literacy [49%, (n = 88)]. The levels of agreement and strong agreement across all barriers and facilitators were similar for participants working in higher or lower income countries. Across all countries, participants rated FDC antihypertensive medications highly valuable for managing patients with non-adherence, (82% reported high or very high value), for patients with high pill burden (80%). Interpretation: Cost and access were the most common barriers to prescribing FDCs across high- and low-income countries. While greater educational support for clinicians was perceived as the leading potential facilitator of FDC use, this seems unlikely to be effective without addressing access.

High ion barrier hydrogel with excellent toughness achieved by directional structures.

Owing to their nontoxicity, environmental friendliness, and high biocompatibility, physically cross-linked hydrogels have become popular research materials; however, their high water content and high free volume, along with the weak bonding interactions inherent to ordinary physically cross-linked hydrogels, limit their application in fields such as flexible devices, packaging materials, and substance transport regulation. Here, a structural barrier approach based on directional freezing-assisted salting out was proposed, and the directional structure significantly enhanced the barrier performance of the hydrogel. When the direction of substance diffusion was perpendicular to the pore channel structure of the directional freezing-PVA hydrogel (DFPVA), the Cl- transmission rate was 57.2% for the uniform freezing-PVA hydrogel (UFPVA). By adjusting the concentration of the salting-out solution and the salting-out time, the crystallinity and crystal domain size of the hydrogel could be further changed, optimizing and regulating the barrier performance of the hydrogel, with the best Cl- unit permeability being 36.02 mg mm per cm2 per day. Additionally, DFPVA had excellent mechanical properties (stress of 6.47 ± 1.04 MPa, strain of 625.85 ± 61.58%, toughness of 25.77 ± 3.72 MPa). Due to the barrier and mechanical properties of the direct structure, DFPVA is suitable as a drug carrier for slow drug release in vitro.

High-nitrogen-induced γ-aminobutyric acid triggers host immunity and pathogen oxidative stress tolerance in tomato and Ralstonia solanacearum interaction.

Soil nitrogen (N) significantly influences the interaction between plants and pathogens, yet its impact on host defenses and pathogen strategies via alterations in plant metabolism remains unclear. Through metabolic and genetic studies, this research demonstrates that high-N-input exacerbates tomato bacterial wilt by altering γ-aminobutyric acid (GABA) metabolism of host plants. Under high-N conditions, the nitrate sensor NIN-like protein 7 (SlNLP7) promotes the glutamate decarboxylase 2/4 (SlGAD2/4) transcription and GABA synthesis by directly binding to the promoters of SlGAD2/4. The tomato plants with enhanced GABA levels showed stronger immune responses but remained susceptible to Ralstonia solanacearum. This led to the discovery that GABA produced by the host actually heightens the pathogen's virulence. We identified the R. solanacearum LysR-type transcriptional regulator OxyR protein, which senses host-derived GABA and, upon interaction, triggers a response involving protein dimerization that enhances the pathogen's oxidative stress tolerance by activating the expression of catalase (katE/katGa). These findings reveal GABA's dual role in activating host immunity and enhancing pathogen tolerance to oxidative stress, highlighting the complex relationship between tomato plants and R. solanacearum, influenced by soil N status.

Comparison of Different Animal Models in Hindlimb Functional Recovery after Acute Limb Ischemia-Reperfusion Injury.

Acute limb ischemia (ALI) is a sudden lack of blood flow to a limb, primarily caused by arterial embolism and thrombosis. Various experimental animal models, including non-invasive and invasive methods, have been developed and successfully used to induce limb ischemia-reperfusion injuries (L-IRI). However, there is no consensus on the methodologies used in animal models for L-IRI, particularly regarding the assessment of functional recovery. The present study aims to compare different approaches that induce L-IRI and determine the optimal animal model to study functional limb recovery. In this study, we applied a pneumatic cuff as a non-invasive method and ligated the aorta, iliac, or femoral artery as invasive methods to induce L-IRI. We have measured grip strength, motor function, creatine kinase level, inflammatory markers such as nuclear factor NF-κB, interleukin-6 (IL-6), hypoxia markers such as hypoxia-induced factor-1α (HIF-1α), and evaluated the muscle injury with hematoxylin and eosin (H&E) staining in Sprague Dawley rats after inducing L-IRI. The pneumatic pressure cuff method significantly decreased the muscle strength of the rats, causing the loss of ability to hold the grid and inducing significant limb function impairment, while artery ligations did not. We conclude from this study that the tourniquet cuff method could be ideal for studying functional recovery after L-IRI in the rat model.

ent-Kaurane diterpenoids from Isodon henryi and their anti-inflammatory activities.

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.

[Intervention of traditional Chinese medicine in spermatogenic epithelium injury by regulating the ferroptosis pathway: Advances in studies].

The incidence of male infertility has been increasing year by year, and one of the major causes is testicular spermatogenic epithelial injury, which affects the spermatogenic function of the testis. Ferroptosis is a novel mode of cell death and plays an important role in testicular cell injury. Some traditional Chinese medicines can intervene in the progression of testicular injury by regulating the ferroptosis pathway in testicular spermatogenic epithelia. This paper focuses on the effect of traditional Chinese drugs in regulating the ferroptosis pathway in testicular cells, and summarizes the advances in the studies of traditional Chinese medicines in the treatment of testicular spermatogenic epithelial injury, aiming to provide a theoretical basis for the selection of relevant medicines and their clinical application.