Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPARα administration.

Neuropathic pain (NP) is usually treated with analgesics and symptomatic therapy with poor efficacy and numerous side effects, highlighting the urgent need for effective treatment strategies. Recent studies have reported an important role for peroxisome proliferator-activated receptor alpha (PPARα) in regulating metabolism as well as inflammatory responses. Through pain behavioral assessment, we found that activation of PPARα prevented chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia. In addition, PPARα ameliorated inflammatory cell infiltration at the injury site and decreased microglial activation, NOD-like receptor protein 3 (NLRP3) inflammasome production, and spinal dendritic spine density, as well as improved serum and spinal cord metabolic levels in mice. Administration of PPARα antagonists eliminates the analgesic effect of PPARα agonists. PPARα relieves NP by inhibiting neuroinflammation and functional synaptic plasticity as well as modulating metabolic mechanisms, suggesting that PPARα may be a potential molecular target for NP alleviation. However, the effects of PPARα on neuroinflammation and synaptic plasticity should be further explored.

Combining fecal 16 S rRNA sequencing and spinal cord metabolomics analysis to explain the modulatory effect of PPARα on neuropathic pain.

BACKGROUND: Existing evidence suggests that the composition of the gut microbiota is associated with neuropathic pain (NP), but the mechanistic link is elusive. Peroxisome proliferator-activated receptor α (PPARα) has been shown to be a pharmacological target for the treatment of metabolic disorders, and its expression is also involved in inflammatory regulation. The aim of this study was to investigate the important modulatory effects of PPARα on gut microbiota and spinal cord metabolites in mice subjected to chronic constriction injury. METHODS: We analyzed fecal microbiota and spinal cord metabolic alterations in mice from the sham, CCI, GW7647 (PPARα agonist) and GW6471 (PPARα antagonist) groups by 16 S rRNA amplicon sequencing and untargeted metabolomics analysis. On this basis, the intestinal microbiota and metabolites that were significantly altered between treatment groups were analyzed in a combined multiomics analysis. We also investigated the effect of PPARα on the polarization fractionation of spinal microglia. RESULTS: PPARα agonist significantly reduce paw withdrawal threshold and paw withdrawal thermal latency, while PPARα antagonist significantly increase paw withdrawal threshold and paw withdrawal thermal latency. 16 S rRNA gene sequencing showed that intraperitoneal injection of GW7647 or GW6471 significantly altered the abundance, homogeneity and composition of the gut microbiome. Analysis of the spinal cord metabolome showed that the levels of spinal cord metabolites were shifted after exposure to GW7647 or GW6471. Alterations in the composition of gut microbiota were significantly associated with the abundance of various spinal cord metabolites. The abundance of Licheniformes showed a significant positive correlation with nicotinamide, benzimidazole, eicosanoids, and pyridine abundance. Immunofluorescence results showed that intraperitoneal injection of GW7647 or GW6471 altered microglial activation and polarization levels. CONCLUSION: Our study shows that PPARα can promote M2-type microglia polarization, as well as alter gut microbiota and metabolites in CCI mice. This study enhances our understanding of the mechanism of PPARα in the treatment of neuropathic pain.

Advances in the differentiation of pluripotent stem cells into vascular cells.

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.

Emerging roles of miRNAs in neuropathic pain: From new findings to novel mechanisms.

Neuropathic pain, which results from damage to the somatosensory nervous system, is a global clinical condition that affects many people. Neuropathic pain imposes significant economic and public health burdens and is often difficult to manage because the underlying mechanisms remain unclear. However, mounting evidence indicates a role for neurogenic inflammation and neuroinflammation in pain pattern development. There is increasing evidence that the activation of neurogenic inflammation and neuroinflammation in the nervous system contribute to neuropathic pain. Altered miRNA expression profiles might be involved in the pathogenesis of both inflammatory and neuropathic pain by regulating neuroinflammation, nerve regeneration, and abnormal ion channel expression. However, the lack of knowledge about miRNA target genes prevents a full understanding of the biological functions of miRNAs. At the same time, an extensive study on exosomal miRNA, a newly discovered role, has advanced our understanding of the pathophysiology of neuropathic pain in recent years. This section provides a comprehensive overview of the current understanding of miRNA research and discusses the potential mechanisms of miRNAs in neuropathic pain.

A new δ-valerolactone produced by marine Streptomyces sp. YIM 13591.

A new δ-valerolactone compound, named 8-hydroxy invictolide 2 (1), a new natural product 4-hydroxy-3,5-dimethyl-6-(pentan-2-yl) tetrahydro-2H-pyran-2-one (2) together with four known compounds cyclo (L-Pro-L-Tyr) (3), cyclo (D-Pro-L-Tyr) (4), acetyltryptophan methyl ester (5), 2-aminobenzoic acid (6) were isolated from marine Streptomyces sp. YIM 13591. Their structures were elucidated by NMR spectroscopic data, HRESIMS and specific rotation, and the absolute configurations of the stereo centre in lactone ring 1 and 2 were further confirmed by electronic circular dichroism (ECD) calculation. The antimicrobial effects of these compounds were evaluated by the paper diffusion method.

Attapulgite Structure Reset to Accelerate the Crystal Transformation of Isotactic Polybutene.

Isotactic polybutene (iPB) has a wide application in the water pipe field. However, the most valuable form I, needs 7 days to complete the transformation. In this study, the attapulgite (ATP), which produces lattice matching of the iPB form I, was selected to prepare an iPB/ATP composite. The Fischer-Tropsch wax (FTW) was grafted with maleic anhydride to obtain MAFT, and the ATP structure was reset by reactions with MAFT to the prepared FATP, which improved the interface compatibility of the ATP and iPB. The Fourier transform infrared spectroscopy (FT-IR) and the water contact angle test confirmed the successful synthesis of FATP. X-ray diffraction (XRD) verified that the graft of MAFT did not affect the crystal structure of ATP. The iPB + 5% FATP had the maximum flexural strength, which was 12.45 Mpa, and the flexural strength of the iPB + 5% FATP annealing for 1 day was much higher than others. Scanning electron microscope (SEM) photographs verified that FATP and iPB had good interface compatibility. The crystal transformation behavior indicated that the iPB + 5% FATP had the fastest crystal transformation rate, which proved that the reset structure, ATP, greatly accelerated the crystal transformation of iPB. This was a detailed study on the effect of lattice matching, interfacial compatibility and internal lubrication of the reset structure, ATP, in the nucleation and growth stages of iPB form I. The result was verified by XRD, differential scanning calorimetry (DSC), Avrami kinetics and polarizing microscope (POM) analysis.

Astragalin attenuates AlCl3/D-galactose-induced aging-like disorders by inhibiting oxidative stress and neuroinflammation.

Astragalin (AST) is a natural flavonoid with excellent antioxidant and anti-inflammatory activities. However, whether AST is an effective chemical for neuronal protection and its underlying mechanisms remain to be elucidated. In this study, we established a mouse model of cognitive impairment and aging-like phenotype induced by sequential administration of AlCl3 and D-galactose (Gal). We found that AST effectively ameliorated cognitive impairment in the model mice and improved their learning and memory performance in the Morris water maze (MWM) test. AlCl3/Gal-induced activation of astrocytes and microglia and inflammation were observed by immunohistochemistry and immunofluorescence, but could be attenuated by AST. In addition, alterations in oxidative stress-regulating enzymes or markers, including T-SOD, T-AOC, CAT, GSH-Px, and MDA, as well as the pro-inflammatory factors TNF-α, IL-1ß, and IL-6, were restored. At the mechanistic level, AlCl3/Gal-intoxicated mice showed a significant elevation of Notch/HES-1 and NF-κB signaling axis corresponding to microglia activation and inflammation. AST attenuated the activation of Notch/HES-1 and NF-κB signaling axis, thus reducing the inflammation. In summary, AST is a promising natural product to protect neurons from toxin-induced injury, indicating its therapeutic potential for neurological disorders.

Six 19,20-epoxycytochalasans from endophytic Diaporthe sp. RJ-47.

Two new cytochalasins, deacetyl-19-epi-cytochalasin P1 (1), deacetyl-19,20-epoxycytochalasin D (2) were isolated from the endophytic fungus Diaporthe sp. RJ-47, along with four known compounds deacetyl-5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (3), 19,20-epoxycytochalasin Q (4), 19,20-epoxycytochalasin C (5) and deacetyl-19,20-epoxy cytochalasin C (6). Their structures were unambiguously elucidated on the basis of the comprehensive analysis of extensive spectroscopic data. The antimicrobial effects of these compounds were evaluated.

HTRPCA: Hypergraph Regularized Tensor Robust Principal Component Analysis for Sample Clustering in Tumor Omics Data.

In recent years, clustering analysis of cancer genomics data has gained widespread attention. However, limited by the dimensions of the matrix, the traditional methods cannot fully mine the underlying geometric structure information in the data. Besides, noise and outliers inevitably exist in the data. To solve the above two problems, we come up with a new method which uses tensor to represent cancer omics data and applies hypergraph to save the geometric structure information in original data. This model is called hypergraph regularized tensor robust principal component analysis (HTRPCA). The data processed by HTRPCA becomes two parts, one of which is a low-rank component that contains pure underlying structure information between samples, and the other is some sparse interference points. So we can use the low-rank component for clustering. This model can retain complex geometric information between more sample points due to the addition of the hypergraph regularization. Through clustering, we can demonstrate the effectiveness of HTRPCA, and the experimental results on TCGA datasets demonstrate that HTRPCA precedes other advanced methods. This paper proposes a new method of using tensors to represent cancer omics data and introduces hypergraph items to save the geometric structure information of the original data. At the same time, the model decomposes the original tensor into low-order tensors and sparse tensors. The low-rank tensor was used to cluster cancer samples to verify the effectiveness of the method.

Chemical constituents from the stems of Acanthopanax senticosus with their cytotoxic activities.

A new coumestan named 7,5'-dihydroxy-4'-(3''-hydroxy-3''-methyl-trans-isobut-1''-enyl) coumestan (1), together with five known compounds (2-6), was isolated from the EtOAc-soluble extract of the stems of Acanthopanax senticosus. Their structures were elucidated based on extensive spectroscopic analyses. All the isolates were evaluated for in vitro cytotoxic activities against four human cancer cells including HepG2, A549, HeLa and MCF-7. Among them, the new compound 1 was found to exhibit significant cytotoxic activity on HeLa cells with IC50 value of 6.5 µM.

Phenotypic and functional comparison of rat enteric neural crest-derived cells during fetal and early-postnatal stages.

In our previous study, we showed that with increasing time in culture, the growth characteristics of enteric neural crest-derived cells (ENCCs) change, and that the proliferation, migration and neural differentiation potential of these cells in vitro notably diminish. However, there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo. In this study, we isolated fetal (embryonic day 14.5) and postnatal (postnatal day 2) ENCCs from the intestines of rats. Fetal ENCCs had greater maximum cross-sectional area of the neurospheres, stronger migration ability, and reduced apoptosis, compared with postnatal ENCCs. However, fetal and postnatal ENCCs had a similar differentiation ability. Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung's disease. In these rats with Hirschsprung's disease, the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs. These findings suggest that, compared with postnatal ENCCs, fetal ENCCs exhibit higher survival and proliferation and migration abilities, and are therefore a more appropriate seed cell for the treatment of Hirschsprung's disease. This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (approval No. 2016086) on March 3, 2016.

Targeting Mitochondrial Metabolism and RNA Polymerase POLRMT to Overcome Multidrug Resistance in Cancer.

Clinically, the prognosis of tumor therapy is fundamentally affected by multidrug resistance (MDR), which is primarily a result of enhanced drug efflux mediated by channels in the membrane that reduce drug accumulation in tumor cells. How to restore the sensitivity of tumor cells to chemotherapy is an ongoing and pressing clinical issue. There is a prevailing view that tumor cells turn to glycolysis for energy supply due to hypoxia. However, studies have shown that mitochondria also play crucial roles, such as providing intermediates for biosynthesis through the tricarboxylic acid (TCA) cycle and a plenty of ATP to fuel cells through the complete breakdown of organic matter by oxidative phosphorylation (OXPHOS). High OXPHOS have been found in some tumors, particularly in cancer stem cells (CSCs), which possess increased mitochondria mass and may be depends on OXPHOS for energy supply. Therefore, they are sensitive to inhibitors of mitochondrial metabolism. In view of this, we should consider mitochondrial metabolism when developing drugs to overcome MDR, where mitochondrial RNA polymerase (POLRMT) would be the focus, as it is responsible for mitochondrial gene expression. Inhibition of POLRMT could disrupt mitochondrial metabolism at its source, causing an energy crisis and ultimately eradicating tumor cells. In addition, it may restore the energy supply of MDR cells to glycolysis and re-sensitize them to conventional chemotherapy. Furthermore, we discuss the rationale and strategies for designing new therapeutic molecules for MDR cancers by targeting POLRMT.

Isotactic Polybutene-1/Bamboo Powder Composites with Excellent Properties at Initial Stage of Molding.

Isotactic polybutylene-1 (iPB) has lots of advantages and is best used as hot water pipe. However, to transform into stable crystal form I, the iPB needs as long as 7 days. In this process, the irreversible damage brings great difficulties to the use of the iPB. The method which convert it directly into crystal I has shortcomings such as being requiring complex operation and being expensive. In this study, an innovative idea was put forward, not paying attention to the crystal transformation of iPB but only focusing on reducing the time it can be applied. In this study, bamboo powder was modified by the silane coupling agent KH570 (KBP) to prepare iPB/KBP composite. The infiltration test and Fourier transform infrared (FTIR) analysis showed that the hydrophilicity of KBP is greatly reduced, which can greatly improve the compatibility of the iPB and KBP. The tensile strength, tensile modulus, flexural strength, and flexural modulus of the composites storage for 3 days is equal to the pure iPB with storage 7 days with the KBP additions of 3%, 3%, 7%, and 5%, respectively. The heat deformation temperature (HDT) of the composite with 3% KBP after 1-day storage reached the value of pure iPB storage for 7 days. This provides more space and possibilities for the industrialization of the iPB. The crystallization behavior of iPB/KBP composites proves that the addition of KBP accelerates the crystallization rate of iPB, but the crystallinity of the iPB/KBP composites is not changed. The SEM photograph of iPB/KBP composites showed that when the KBP addition was low the compatibility between KBP and iPB was good. When the KBP addition was increased the agglomeration of KBP in the iPB was very obvious, which leads to the poor mechanical properties of the composite.

[Comparison of the Control of Sedimentary Phosphorus Release Using Zirconium-, Lanthanum-, and Lanthanum/Zirconium-Modified Zeolites as Sediment Amendments].

In this study, the adsorption characteristics of phosphate on zirconium-modified zeolite (ZrMZ), lanthanum-modified zeolite (LaMZ) and lanthanum/zirconium-modified zeolite (LaZrMZ) were comparatively investigated, and the effect of ZrMZ, LaMZ, and LaZrMZ addition on the mobilization of phosphorus (P) in sediments was comparatively studied. Results showed that the phosphate adsorption capacity decreased in the order of LaZrMZ > LaMZ > ZrMZ. The addition of LaZrMZ, LaMZ, and ZrMZ in sediments all could effectively reduce the concentrations of soluble reactive P (SRP) in the overlying and pore waters. Furthermore, the addition of LaZrMZ, LaMZ and ZrMZ all could decrease the amount of mobile P in sediments, and the reduction rate decreased in the order of LaMZ > LaZrMZ > ZrMZ. The amendment of sediments with LaZrMZ, LaMZ, and ZrMZ all could lead to a decrease in the amount of water-soluble P (WSP), algal available P (AA-P) and iron oxide-filter paper extractable P (FeO-P) in the sediments. The reduction rate of WSP and AA-P decreased in the order of LaMZ > LaZrMZ > ZrMZ, and the reduction rate of FeO-P decreased in the order of LaZrMZ > ZrMZ > LaMZ. The addition of LaZrMZ and LaMZ both could reduce the content of readily desorbed P (RDP), and the reduction rate decreased in the order of LaMZ>LaZrMZ. The LaZrMZ and ZrMZ amendments both could decrease the concentration of NaHCO3 extractable P (Olsen-P) in sediments, and the reduction rate decreased in the order of LaZrMZ>ZrMZ. The results of this study demonstrate that the addition of ZrMZ, LaMZ, and LaZrMZ in sediments all could effectively intercept the upward mobilization of sedimentary P to the overlying water, and LaZrMZ is a very promising amendment for the control of the internal P loading from the point of view of both phosphate adsorption ability and bioavailable P immobilization efficiency.

Cervical Spinal Involvement in a Chinese Pedigree With Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy Caused by a 3' Untranslated Region Mutation of COL4A1 Gene.

Background and Purpose- Pontine autosomal dominant microangiopathy and leukoencephalopathy, a recently defined subtype of cerebral small vessel disease, is associated with mutations in COL4A1 (collagen type IV alpha 1 chain) 3' untranslated region. We here describe a pontine autosomal dominant microangiopathy and leukoencephalopathy pedigree with COL4A1 mutation presenting both pontine and cervical spinal cord involvement. Methods- For the diagnostic purpose, brain and spinal magnetic resonance imaging scanning, skin biopsy, and whole-exome sequencing were performed on the patients in the pedigree. Suspected pathogenic variants were further confirmed by cosegregation analysis using Sanger sequencing in the family members. Results- We identified a mutation located at the binding site of miR-29 (microRNA-29) in 3' untranslated region of COL4A1(c.*32G>A). The pontine autosomal dominant microangiopathy and leukoencephalopathy patients in this pedigree carried this variant, whereas other healthy family members but one did not. Magnetic resonance imaging showed lesions in the pons, white matter, and cervical spinal cord. Skin biopsy revealed thickened basal lamina in vessels. Conclusions- For the first time, we reported cervical spinal involvement in pontine autosomal dominant microangiopathy and leukoencephalopathy and expanded the clinical spectrum of this disease.

[Effect of Zirconium-Modified Zeolite Addition on Migration and Transformation of Phosphorus in River Sediments Under Static and Hydrodynamic Disturbance Conditions].

In this study, the effect of the addition of zirconium-modified zeolite (ZrMZ) on the migration and transformation of phosphorus (P) in river sediments under static and hydrodynamic disturbance conditions was studied using sediment core incubation experiments. Results showed that, whether under static or hydrodynamic disturbance condition, the ZrMZ amendment suppressed the release of SRP from sediments into the overlying water. Furthermore, the addition of ZrMZ to the upper sediment (0-10 mm) not only resulted in the decrease of the dissoluble reactive P (SRP) concentration in the overlying water at a depth of 0-30 mm, but also led to the decrease of the diffusion flux of SRP from the pore water to the overlying water across the sediment-water interface (SWI). In addition, the ZrMZ amendment induced the transformation of the redox-sensitive P (BD-P) and HCl extractable P (HCl-P) into the metal oxide-bound P (NaOH-rP) and residual P (Res-P), thus resulting in the reduction of mobile P (sum of NH4Cl extractable P and BD-P) in the top 10 mm of sediment. In addition, the addition of ZrMZ into the top 10 mm of sediment resulted in reduction of the content of mobile P in 10-20 mm of sediment. Furthermore, the effect of ZrMZ addition on the migration and transformation of P in sediments under hydrodynamic disturbance condition had a certain difference from that under static condition. The presence of hydrodynamic disturbance enhanced the immobilization efficiency of SRP in the pore water at a depth of 0-20 mm by the ZrMZ amendment, and also increased the reduction efficiency of the SRP diffusion flux from the pore water to the overlying water across the SWI by the ZrMZ amendment. However, the efficiency of the control of SRP release from sediments to the overlying water by the ZrMZ amendment was slightly reduced by the hydrodynamic disturbance. The reductions of mobile P in the top sediment, SRP in the pore water as well as the diffusion flux of SRP from the pore water to the overlying water across the SWI played a key role in the control of SRP release from sediments to the overlying water by the ZrMZ amendment. Results of this work indicate that ZrMZ is a very promising amendment for the control of SRP release from river sediments under static and hydrodynamic disturbance conditions.

Activated mTOR signaling pathway in myofibers with inherited metabolic defect might be an evidence for mTOR inhibition therapies.

BACKGROUND: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles. METHODS: We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry. RESULTS: Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U = 2.000, P = 0.024; NC vs. MM: U = 6.000, P = 0.043). Likewise, p-S6/S6 was also up-regulated in muscles from all three subgroups of IMMs (NC vs. LSD, U = 0.000, P = 0.006; NC vs. PD, U = 0.000, P = 0.006; NC vs. MM, U = 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U = 0.000, P = 0.002) or basophilic materials (U = 0.000, P = 0.002). CONCLUSION: The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs.

Clinical feature and outcome of late-onset cobalamin C disease patients with neuropsychiatric presentations: a Chinese case series.

OBJECTIVE: The Cobalamin C (cblC) disease is an inborn error of cobalamin metabolism. Late-onset cblC disease was diagnosed in patients having overt symptoms after 4 years of age. The late-onset cblC disease patients were rare and easily misdiagnosed. This study analyzed the clinical presentations, gene mutations, and treatments of Chinese patients with late-onset cblC disease. METHODS: The clinical data of 26 Han Chinese patients diagnosed with late-onset cblC disease were retrospectively analyzed. All patients underwent serum homocysteine level exam, urine concentrations of organic acids measurement, neuroimaging scans, gene analysis, and treatments evaluations. RESULTS: The mean age at disease onset and diagnosis was 17.8±7.0 years. The most frequent neuropsychiatric disturbances were lower limb weakness (50%), psychiatric disturbances (46.2%), and gait instability (42.3%). The mean methylmalonic acid level in urine was 107.4±56.6 µmol/L, and mean serum total homocysteine was 105.4±41.0 µmol/L. The most common abnormal radioimaging changes were observed in the spinal cord (88%) and brain (32%). Scoliosis was detected in 85.7% of patients. The methylmalonic aciduria and homocystinuria type C protein gene analysis showed that c.482G>A (57.7%) and c.609G>A (34.6%) mutations were the most frequent genotypes. After treatments with hydroxycobalamin, betaine, folic acid, L-carnitine, and compound vitamin B, the clinical features and biochemical parameters of patients with late-onset cblC disease were found to be alleviated. CONCLUSION: In our late-onset cblC disease cases, lower limb weakness, psychiatric disturbances, and gait instability were the most frequent manifestations. Patients responded well to the drug treatments with hydrocobalamin and betaine. When juvenile or adult patients with hyperhomocysteinemia present with neurological symptoms, cblC disease needs to be considered.