ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

Objective To investigate the diagnostic value of computed tomography (CT) grading in evaluating sacroiliac joint lesions and the extent of joint injury in patients with ankylosing spondylitis (AS) so as to provide evidence-based evidence for CT imaging diagnosis and severity evaluation of AS. Methods A total of 107 patients with AS admitted to the hospital between December 2020 and December 2024 were selected. All patients underwent X-ray and CT examinations, and were graded based on the examination results. The diagnostic value of X-ray and CT in sacroiliac joint lesions and the severity of joint injury in patients with AS was compared. Results The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, ankylosis, and soft tissue swelling using CT (90.65%、100.00%、87.85%、41.12%、56.07%、22.43%、33.64%) were higher than those using X-ray (75.70%、84.11%、58.88%、32.71%、48.60%、10.28%、7.48%) (P<0.05). The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, joint space narrowing, joint space widening, ankylosis, and soft tissue swelling using CT combined with X-ray (97.20%、10.00%、95.33%、57.94%、73.83%、34.58%、39.25%) were higher than those using CT or X-ray alone (P<0.05). The comparison of the detection of grade I, grade II and grade III joint injury degrees by CT, X-ray and combined examination showed statistically significant differences (P<0.05). The detection rates of grades I and II joint injuries using CT (26.17%、35.51%) were higher than those using X-ray (14.95%、22.43%) (P<0.05). The detection rates of grades 0, I, II, and III joint injury by the combined examination of X-ray and CT were higher than those using X-ray alone (P<0.05). Conclusion CT has greater diagnostic value for sacroiliac joint lesions and severity of joint injury in patients with AS, and allowing for more accurate in AS grading, and combined it with X-ray further improves diagnostic efficacy.

Objective To investigate the diagnostic value of computed tomography (CT) grading in evaluating sacroiliac joint lesions and the extent of joint injury in patients with ankylosing spondylitis (AS) so as to provide evidence-based evidence for CT imaging diagnosis and severity evaluation of AS. Methods A total of 107 patients with AS admitted to the hospital between December 2020 and December 2024 were selected. All patients underwent X-ray and CT examinations, and were graded based on the examination results. The diagnostic value of X-ray and CT in sacroiliac joint lesions and the severity of joint injury in patients with AS was compared. Results The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, ankylosis, and soft tissue swelling using CT (90.65%、100.00%、87.85%、41.12%、56.07%、22.43%、33.64%) were higher than those using X-ray (75.70%、84.11%、58.88%、32.71%、48.60%、10.28%、7.48%) (P<0.05). The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, joint space narrowing, joint space widening, ankylosis, and soft tissue swelling using CT combined with X-ray (97.20%、10.00%、95.33%、57.94%、73.83%、34.58%、39.25%) were higher than those using CT or X-ray alone (P<0.05). The comparison of the detection of grade I, grade II and grade III joint injury degrees by CT, X-ray and combined examination showed statistically significant differences (P<0.05). The detection rates of grades I and II joint injuries using CT (26.17%、35.51%) were higher than those using X-ray (14.95%、22.43%) (P<0.05). The detection rates of grades 0, I, II, and III joint injury by the combined examination of X-ray and CT were higher than those using X-ray alone (P<0.05). Conclusion CT has greater diagnostic value for sacroiliac joint lesions and severity of joint injury in patients with AS, and allowing for more accurate in AS grading, and combined it with X-ray further improves diagnostic efficacy.

Objective To investigate the diagnostic value of computed tomography (CT) grading in evaluating sacroiliac joint lesions and the extent of joint injury in patients with ankylosing spondylitis (AS) so as to provide evidence-based evidence for CT imaging diagnosis and severity evaluation of AS. Methods A total of 107 patients with AS admitted to the hospital between December 2020 and December 2024 were selected. All patients underwent X-ray and CT examinations, and were graded based on the examination results. The diagnostic value of X-ray and CT in sacroiliac joint lesions and the severity of joint injury in patients with AS was compared. Results The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, ankylosis, and soft tissue swelling using CT (90.65%、100.00%、87.85%、41.12%、56.07%、22.43%、33.64%) were higher than those using X-ray (75.70%、84.11%、58.88%、32.71%、48.60%、10.28%、7.48%) (P<0.05). The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, joint space narrowing, joint space widening, ankylosis, and soft tissue swelling using CT combined with X-ray (97.20%、10.00%、95.33%、57.94%、73.83%、34.58%、39.25%) were higher than those using CT or X-ray alone (P<0.05). The comparison of the detection of grade I, grade II and grade III joint injury degrees by CT, X-ray and combined examination showed statistically significant differences (P<0.05). The detection rates of grades I and II joint injuries using CT (26.17%、35.51%) were higher than those using X-ray (14.95%、22.43%) (P<0.05). The detection rates of grades 0, I, II, and III joint injury by the combined examination of X-ray and CT were higher than those using X-ray alone (P<0.05). Conclusion CT has greater diagnostic value for sacroiliac joint lesions and severity of joint injury in patients with AS, and allowing for more accurate in AS grading, and combined it with X-ray further improves diagnostic efficacy.

Tripartite motif-containing (TRIM) family proteins are crucial E3 ubiquitin ligases that have garnered significant attention for their regulatory roles in bone metabolism in recent years. This article reviews the function and regulatory mechanisms of TRIM family proteins in bone metabolism, focusing on their dual roles in bone formation and resorption. It also provides a detailed analysis of signaling pathways and molecular mechanisms by which TRIM family members regulate the activities of osteoblasts and osteoclasts. Research findings suggest that modulating the expression or activity of TRIM family proteins could be beneficial for treating bone diseases such as osteoporosis. This review highlights the molecular mechanisms of TRIM family members in bone physiology and pathology, aiming to provide theoretical basis and scientific guidance for developing novel therapeutic strategies for bone diseases.
Humans ; Ubiquitin-Protein Ligases/physiology* ; Bone and Bones/metabolism* ; Animals ; Tripartite Motif Proteins/physiology* ; Osteoclasts/metabolism* ; Osteoblasts/metabolism* ; Signal Transduction/physiology* ; Osteogenesis/physiology*

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

Through evidence mapping, this paper systematically summarized the research evidence on the use of traditional Chinese medicine(TCM) in treating renal anemia, displaying the distribution of evidence in this field. A systematic search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, Springner, PubMed, Engineering Village, and Web of Science, targeting studies published up to June 30, 2024. The research evidence was summarized and displayed through a combination of graphs, tables, and text. A total of 264 interventional studies, 37 observational studies, and 7 systematic reviews were included. The annual publication volumes related to TCM treatment in renal anemia showed an overall upward trend, with most studies involving sample sizes between 60 and 120 participants(224 articles, 74.42%). Intervention measures were categorized into 21 types, with oral TCM decoctions being the most common medicine(171 times, 56.81%). The use of self-made prescriptions was the most common TCM intervention method. The intervention duration was mainly between 8 weeks and 3 months(239 articles, 79.40%). The most frequently reported TCM syndrome was spleen and kidney Qi deficiency. The top 2 outcome indicators were the anemia indicators and renal injury/renal function markers. However, several issues were identified in these studies, such as insufficient attention to the sources, social/geographical information, and temporal continuity of research subjects in observational research. Randomized controlled trials mostly had a high risk of bias, mainly due to issues such as randomization bias, blinding bias, and failure to register research protocols. The methodology quality of systematic reviews was generally low, mainly due to inadequate inclusion of literature, failure to specify funding sources, and lack of pre-registrations. While the report quality of systematic review was acceptable, there were significant gaps in the reporting of protocols, registration, and funds. The results show that these issues affect the quality of research and the reliability of findings on TCM in treating renal anemia, underscoring the need to address them to conduct higher-quality research and provide more reliable medical evidence for TCM in treating renal anemia.
Humans ; Anemia/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/drug therapy*