Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Near infrared spectroscopy(NIRS)technology combined with chemometrics algorithms has been widely used in quantitative and qualitative analysis of food and medicine.However,traditional chemometrics methods,especially linear classification methods,often yield unsatisfactory results when addressing multi-class classification problems.Convolutional neural network(CNN)is adept at extracting deep-level features from data and suitable for handling non-linear relationships.The modeling performance of CNN depends on the size and diversity of sample,while the collection and preprocessing of NIRS sample data is often time-consuming and labor-intensive.This study proposed a NIRS qualitative analysis method based on data augmentation strategies and CNN.The data augmentation strategy included two steps.Firstly,applying Bootstrap resampling and generative adversarial network(GAN)methods to augment three NIRS datasets(Medicine,coffee and grape).Secondly,combining the original samples(Y)with the Bootstrap augmented samples(B)and GAN augmented samples(G)to obtain three augmented datasets(Y-B,Y-G and Y-B-G).Based on this,a CNN model structure suitable for these datasets was designed,consisting of 2 one-dimensional convolutional layers,1 max-pooling layer,and 1 fully connected layer.The results showed that compared to the optimal models of partial least squares discriminant analysis(PLS-DA),support vector machine(SVM),and back propagation neural network(BP),the CNN model based on Y-B dataset achieved average accuracy improvements of 3.998%,9.364%,and 4.689%for medicine(Binary classification);the CNN model based on the Y-B-G dataset achieved average accuracy improvements of 6.001%,2.004%,and 7.523%for coffee(7-class classification);and the CNN model based on the Y-B dataset achieved average accuracy improvements of 33.408%,51.994%,and 34.378%for grapes(20-class classification).It was evident that the models established based on data augmentation strategies and CNN demonstrated better classification accuracy and generalization performance with different datasets and classification categories.

Aim To investigate the dynamic changes of neuronal cells at different time points following acute cerebral ischemia-reperfusion injury by establishing a model of brain ischemia-reperfusion injury.Methods Thirty male Sprague-Dawley(SD)rats were ran-domly divided into six groups:sham group and cere-bral ischemia-reperfusion injury(IR)groups at differ-ent time points.Focal cerebral ischemia-reperfusion injury model was established using the middle cerebral artery occlusion(MCAO)technique.The Longa sco-ring method was used to assess neurobehavioral scores in rats.After successful model preparation,routine paraffin sections were made,and TUNEL staining and immunohistochemistry staining with NeuN antibody were performed to observe cell apoptosis and neuronal cell survival,respectively.Immunohistochemistry stai-ning was also performed to investigate the changes in glial fibrillary acidic protein(GFAP)as a marker for astrocytes,ionized calcium-binding adapter molecule 1(IBA-1)as a marker for microglia,and CD31 as a marker for endothelial cells at different time points.Results No significant changes were observed in neu-ronal cells of the sham group at different time points.In the cerebral ischemia-reperfusion injury groups,cell apoptosis was activated at IR3h and increased in quan-tity with morphological damage as time progressed.Ne-uN+neurons showed signs of ischemic injury after IR3h,with abnormal cell morphology.From 12 h,Ne-uN+neurons decreased in a time-dependent manner and reached their peak severity at 24 h.GFAP+astro-cytes decreased significantly after IR3h,while poorly labeled GFAP+astrocytes increased at IR 6 h and al-most disappeared in the infarcted area at 24 h and 48 h.The number of IBA-1+microglia-positive cells de-creased at IR3h,and their volume increased at IR6h.Microglial cell death was observed in the infarcted area at IR12h.CD31+endothelial cells around the infarc-ted cortex and striatum increased significantly after IR3h and persisted until 48 h.Conclusions After cerebral ischemia-reperfusion injury,the number of ap-optotic cells increases with the prolongation of time,and NeuN+neurons exhibit the most severe damage at 24 h.GFAP+astrocytes and microglial cells gradually die over time.The number of CD31+endothelial cells increases significantly around the infarcted cortex and striatum after 3 h of reperfusion and persists until 48 h.

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.
Rats ; Animals ; Rats, Sprague-Dawley ; Brain Ischemia/drug therapy* ; Reperfusion Injury/metabolism* ; Infarction, Middle Cerebral Artery ; Neuronal Plasticity ; Reperfusion

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease

BACKGROUND: Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR). METHODS: A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics. RESULTS: A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum ( P =0.0006) and left fusiform gyrus ( P =0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group. CONCLUSIONS The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.
Humans ; Depressive Disorder, Major/drug therapy* ; Schizophrenia/pathology* ; Brain/pathology* ; Prefrontal Cortex ; Frontal Lobe ; Magnetic Resonance Imaging/methods*

This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury. The model of cerebral IR injury was established using the middle cerebral artery occlusion method. Fluorocitrate(FC), an inhibitor of astrocyte activation, was applied to inhibit astrocyte activation. Rats were randomly divided into a sham group, a model group, a XXMD group, a XXMD+FC group, and a XXMD+Vehicle group. Neurobehavioral changes at 24 hours after cerebral IR injury, cerebral infarction, histopathological changes observed through HE staining, submicroscopic structure of astrocytes observed through transmission electron microscopy, fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence, and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group. The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group. The XXMD group, the XXMD+FC group, and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats. The pathological changes in the brain were evident in the model group, while the XXMD group, the XXMD+FC group, and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats. The submicroscopic structure of astrocytes in the model group showed significant swelling, whereas the XXMD group, the XXMD+FC group, and XXMD+Vehicle group protected the submicroscopic structure of astrocytes. The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group. However, the XXMD group, the XXMD+FC group, and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1. The combination of XXMD and FC showed a more pronounced effect. These results indicate that XXMD can improve cerebral IR injury, possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.
Rats ; Animals ; Astrocytes ; Brain Ischemia/metabolism* ; Brain ; Reperfusion Injury/metabolism* ; Infarction, Middle Cerebral Artery