Application of Intestinal Barrier Molecules in the Diagnosis of Acute Cellular Rejection After Intestinal Transplantation.

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.

Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency.

Aromatic L-amino acid decarboxylase deficiency results in decreased neurotransmitter levels and severe motor dysfunction. Twenty-six patients without head control received bilateral intraputaminal infusions of a recombinant adeno-associated virus type 2 vector containing the human aromatic L-amino acid decarboxylase gene (eladocagene exuparvovec) and have completed 1-year evaluations. Rapid improvements in motor and cognitive function occurred within 12 months after gene therapy and were sustained during follow-up for >5 years. An increase in dopamine production was demonstrated by positron emission tomography and neurotransmitter analysis. Patient symptoms (mood, sweating, temperature, and oculogyric crises), patient growth, and patient caretaker quality of life improved. Although improvements were observed in all treated participants, younger age was associated with greater improvement. There were no treatment-associated brain injuries, and most adverse events were related to underlying disease. Post-surgery complications such as cerebrospinal fluid leakage were managed with standard of care. Most patients experienced mild to moderate dyskinesia that resolved in a few months. These observations suggest that eladocagene exuparvovec treatment for aromatic L-amino acid decarboxylase deficiency provides durable and meaningful benefits with a favorable safety profile.

Cerebellar deep brain stimulation for movement disorders.

Deep brain stimulation (DBS) conventionally target at basal ganglia or thalamic structures, modulating nodal points in the cortico-basal ganglia circuit, in order to effectively treat various movement disorders, including Parkinson's disease, tremor and dystonia (especially mobile type dystonia). However, there are still some other movement disorders, such as dystonia (especially fixed type dystonia), ataxia and freezing of gait, which are not responding well to the current DBS therapy. Cerebellum, similar to basal ganglia, also plays a critical role in the pathophysiology of movement disorders. Deep cerebellar structures, such as dentate nucleus or superior cerebellar peduncle, are noticed for their potential role as treatment targets in movement disorders in recent years. With increasing evidences of animal DBS experiments, recent clinical human subject studies reported that some movement disorders patients not responding to DBS with conventional targets, may benefit significantly from cerebellar DBS. These pioneer study results are invaluable for understanding the clinical use of cerebellar DBS for treatment of movement disorders. We review the recent data of cerebellar DBS performed by different groups and summarize the indications, surgical targets, programming details and outcomes in these clinical reports. We then synthesize the current pathophysiological study of cerebellum on different movement disorders and discuss the potential mechanism of action of cerebellar DBS. In addition to basal ganglia, it is important to study new DBS targets in the cerebellum for more comprehensive treatment of movement disorders.

Long-term efficacy of bilateral subthalamic deep brain stimulation in the parkinsonism of SCA 3: A rare case report.

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited disorder that manifests as a mixture of cerebellar ataxia, parkinsonism, and polyneuropathy; in type IV SCA3, pure parkinsonism is the only symptom. Currently, no disease-modifying treatment is available, but variable responses to antiparkinsonism agents have been reported. However, the benefits of deep brain stimulation (DBS) for treating parkinsonism in this subtype of SCA3 remain unclear. METHODS: A 39-year-old male patient with a rare disorder of type IV SCA3 presented with pure parkinsonism including unilateral resting tremor, rigidity, and bradykinesia at the age of 30 years. Young-onset Parkinson disease was diagnosed at the age of 32 years. His family history revealed a mild ataxia in his father since the age of 55 years. Genetic testing confirmed an expanded CAG repeated number, with 66 in this case and 63 in his father for SCA3 mutation. Excellent response to levodopa and dopamine agonists in the first 3 years was noted, but wearing-off phenomena, levodopa-induced dyskinesia, and severe impulse control disorders later developed. To alleviate drug-induced complications, he received bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in the absence of cerebellar signs, depression, and cognitive impairment. RESULTS: As of 2019, no impulsive control disorders, motor fluctuations, or DBS-related complications were observed during a 4-year follow-up, with 66% Unified Parkinson's Disease Rating Scale Part III reduction at medication OFF state noted, whereas levodopa equivalent daily dosage decreased by almost half. CONCLUSIONS: STN-DBS may be considered as adjunct treatment for severe dopa-related motor/nonmotor complications in patients with parkinsonian phenotype of SCA 3.

Regulation of ZMYND8 to Treat Cancer.

Zinc finger myeloid, nervy, and deformed epidermal autoregulatory factor 1-type containing 8 (Zinc finger MYND-type containing 8, ZMYND8) is a transcription factor, a histone H3-interacting protein, and a putative chromatin reader/effector that plays an essential role in regulating transcription during normal cellular growth. Mutations and altered expression of ZMYND8 are associated with the development and progression of cancer. Increased expression of ZMYND8 is linked to breast, prostate, colorectal, and cervical cancers. It exerts pro-oncogenic effects in breast and prostate cancers, and it promotes angiogenesis in zebrafish, as well as in breast and prostate cancers. In contrast, downregulation of ZMYND8 is also reported in breast, prostate, and nasopharyngeal cancers. ZMYND8 acts as a tumor suppressor in breast and prostate cancers, and it inhibits tumor growth by promoting differentiation; inhibiting proliferation, cell-cycle progression, invasiveness, and metastasis; and maintaining the epithelial phenotype in various types of cancers. These data together suggest that ZMYND8 is important in tumorigenesis; however, the existing data are contradictory. More studies are necessary to clarify the exact role of ZMYND8 in tumorigenesis. In the future, regulation of expression/activity of ZMYND8 and/or its binding partners may become useful in treating cancer.

HDAC Inhibitors and RECK Modulate Endoplasmic Reticulum Stress in Tumor Cells.

In the tumor microenvironment hypoxia and nutrient deprived states can induce endoplasmic reticulum (ER) stress. If ER stress is not relieved, the tumor cells may become apoptotic. Therefore, targeting ER homeostasis is a potential strategy for cancer treatment. Various chemotherapeutic agents including histone deacetylase (HDAC) inhibitors can induce ER stress to cause cell death in cancers. Some HDAC inhibitors can prevent HDAC from binding to the specificity protein 1-binding site of the promoter of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and up-regulate RECK expression. Up-regulation of RECK expression by HDAC inhibitors has been observed in various cancer types. RECK is a tumor and metastasis suppressor gene and is critical for regulating tumor cell invasiveness and metastasis. RECK also modulates ER stress via binding to and sequestering glucose-regulated protein 78 protein, so that the transmembrane sensors, such as protein kinase RNA-like ER kinase are released to activate eukaryotic translational initiation factor 2α phosphorylation and enhance ER stress. Therefore, HDAC inhibitors may directly induce ER stress or indirectly induce this stress by up-regulating RECK in cancer cells.

Ischemic preconditioning increased the intestinal stem cell activities in the intestinal crypts in mice.

BACKGROUND: Ischemic preconditioning (IPC) can protect against ischemia-reperfusion injury in the small intestine. Because intestinal stem cells (ISCs) control the recovery and growth of intestinal villi, this study investigated whether IPC had any effects on the activity of ISCs. MATERIALS AND METHODS: The small intestines of mice were treated with IPC, laparotomy only (sham), or no surgery. The crypt fractions were isolated and the characteristics of ISCs among various groups were compared. The regenerative ability and the number of organoids grown from various crypt fractions were compared. The expression of hypoxia-inducible factor-1α (HIF-1α) and the related proteins of the Wnt-/ß-catenin pathway in the crypt fractions were studied. RESULTS: The IPC group had higher messenger RNA levels of various stem cell markers than the sham group at days 1 and 2 after surgery. The IPC group exhibited greater regenerative activity and more crypt organoids than the sham group (P < 0.05). The expression of HIF-1α, ß-catenin, and phosphoglycogen synthase kinase 3ß was increased in the IPC-treated crypt fractions in vivo and cultured crypt organoid cells with deferoxamine-mimicked hypoxia in vitro. CONCLUSIONS: IPC significantly upregulated the activity of ISCs, possibly through the HIF-1α response and Wnt-/ß-catenin signaling pathway.

Isolated intestinal transplantation for megacystis microcolon intestinal hypoperistalsis syndrome: case report.

MMIHS is a rare congenital disease. It is characterized by distended urinary bladder, small colon and intestinal hypoperistalsis, or aperistalsis with normal morphology. There is no specific treatment for MMIHS, and most patients have to be maintained by TPN, which frequently causes TPN-related liver failure, loss of venous access, or catheter-related sepsis. The prognosis of patients with MMIHS is poor, and most patients die early. Multivisceral transplantation including stomach, duodenum, intestine, and liver has been used for the treatment of patients with MMIHS because these patients often have liver failure. We report an eight-yr-old patient with MMIHS who was treated with isolated intestinal transplantation. She had completely oral intake during the four yr of follow-up. The experience in this case suggests isolated intestinal transplantation may be indicated in selected cases with MMIHS.

Application of three-dimensional imaging to the intestinal crypt organoids and biopsied intestinal tissues.

Two-dimensional (2D) histopathology is the standard analytical method for intestinal biopsied tissues; however, the role of 3-dimensional (3D) imaging system in the analysis of the intestinal tissues is unclear. The 3D structure of the crypt organoids from the intestinal stem cell culture and intestinal tissues from the donors and recipients after intestinal transplantation was observed using a 3D imaging system and compared with 2D histopathology and immunohistochemistry. The crypt organoids and intestinal tissues showed well-defined 3D structures. The 3D images of the intestinal tissues with acute rejection revealed absence of villi and few crypts, which were consistent with the histopathological features. In the intestinal transplant for megacystis microcolon intestinal hypoperistalsis syndrome, the donor's intestinal tissues had well-developed nerve networks and interstitial cells of Cajal (ICCs) in the muscle layer, while the recipient's intestinal tissues had distorted nerve network and the ICCs were few and sparsely distributed, relative to those of the donor. The 3D images showed a clear spatial relationship between the microstructures of the small bowel and the features of graft rejection. In conclusion, integration of the 3D imaging and 2D histopathology provided a global view of the intestinal tissues from the transplant patients.

Valproic acid affected the survival and invasiveness of human glioma cells through diverse mechanisms.

The effects of valproic acid (VPA) on the viability, apoptosis, and invasiveness of two glioma cells (A172 and T98G) and the underlying mechanisms were studied. VPA induced cytotoxicity and apoptosis, and suppressed the invasiveness of both cells. VPA increased the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in A172 cells, but decreased it in T98G cells. siRNA blockade of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression partially reversed VPA-mediated effects in T98G cells, but had no effect on A172 cells. VPA increased the expression of phospho-JNK1 and phospho-ERK1/2 in A172 cells, but decreased it in T98G cells. Inhibition of JNK1 and/or ERK1/2 partially reversed the VPA effects in A172 cells. In conclusion, the effects of VPA (loss of viability, increased apoptosis, and decreased invasiveness) are, at least partly, mediated through the RECK-MMPs pathway in T98G cells and the mitogen-activated protein kinase pathways in A172 cells. The action of VPA seems to be cell type-specific in glioma cells.

Platelet abnormalities in patients with Parkinson's disease undergoing preoperative evaluation for deep brain stimulation.

Normal hemostatic function is important for reduction of the risk of intracranial hemorrhage during stereotactic neurosurgery including deep brain stimulation (DBS) surgery. This study investigates the hemostatic function in patients with Parkinson's disease (PD) undergoing preoperative evaluation for DBS, with emphasis on the number and function of platelets. In 107 PD patients, only one had abnormal activated partial prothrombin time and normal prothrombin time. Among the other 106 patients, six (5.7%) had only thrombocytopenia, seven (6.6%) only prolonged bleeding time (BT), and 14 (13.2%) only prolonged closure time (CT) of platelet function analyzer 100 (PFA-100). Totally, 34 of the 106 patients (32.1%) had at least one of three kinds of platelet abnormalities. No factor was found to be associated with the occurrence of platelet abnormalities except that abnormal platelet group and prolonged BT subgroup had more patients using selegiline and lower UPDRS-III motor subscore with medication off than normal platelet group (p < 0.05). The use of selegiline was significantly correlated with prolonged BT (p = 0.0041) and platelet abnormality (p = 0.0197). Therefore, it is important to have detailed evaluation of the hemostatic function for PD patients undergoing preoperative evaluation for DBS, especially the platelet number and function.

Long-Term Outcomes of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series.

BACKGROUND: Among dystonia patients receiving globus pallidus internus (GPi) deep brain stimulation (DBS), long-term outcomes remain to be established. To report the long-term outcomes of GPi DBS in a patient cohort with idiopathic and acquired dystonia. METHODS: In this long-term follow-up cohort, there were 4 patients with idiopathic dystonia and 2 patients with acquired dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale was used to evaluate 6 consecutive patients preoperatively and at 6 months, 12 months, and the last follow-up. The relationship between etiology and clinical improvement was analyzed. Stimulation parameters were evaluated for similarities and differences among these patients. RESULTS: The mean follow-up of our cohort was 65.3 months (median 40.5 months). The average improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (mean ± SEM) were 56% ± 7.6, 67% ± 6.8 and 66% ± 9.7 at 6 months, 12 months, and the last follow-up, respectively. There was greater improvement during the long-term follow-up in the 4 patients with idiopathic dystonia than in the 2 patients with acquired dystonia. The 2 most ventral electrodes (contact 0 and 1) were activated in all 11 leads in this cohort. The average stimulation intensity, pulse width and frequency were 2.0 ± 0.24 mA, 252 ± 43 µs, and 99 ± 6.0 Hz, respectively. CONCLUSIONS: Isolated dystonia, either monogenic or idiopathic, usually responds better to GPi DBS than to acquired dystonia. Selection of patients by dystonia etiology, accurate placement of DBS leads in GPi targets, and proper stimulation programming are crucial to achieve better long-term outcomes.

Comparison of craniotomy and decompressive craniectomy in severely head-injured patients with acute subdural hematoma.

BACKGROUND: Decompressive craniectomy (DC) is helpful in lowering the intracranial pressure in patients with severe head injuries. However, it is still unclear which surgical approach (DC or craniotomy) is the optimal treatment strategy for severely head-injured patients with acute subdural hematoma (SDH). To clarify this point, we compared the outcomes and complications of the patients with acute SDH and low Glasgow Coma Scale (GCS) score treated with craniotomy or DC. METHODS: We analyzed 102 patients with acute SDH and GCS scores of 4 to 8. Of them, 42 patients (41.2%) were treated with craniotomy and 60 (58.8%) treated with DC for evacuation of hematoma. The demographic and clinical data were analyzed including patient age, sex, injury mechanism, GCS score, pupil size and light reflex, time interval from injury to operation, types of surgical procedures, intracranial findings in pre- and postoperative computed tomography scan, intracranial pressure, complications, requirement of permanent cerebrospinal fluid diversion, and Glasgow Outcome Scale score after at least 1 year of follow-up. RESULTS: The craniotomy and DC groups showed no difference in the demographic and clinical data. There was no difference in the outcomes and complication rates between these two groups except that the DC group had higher mortality than the craniotomy group (23.3% vs. 7.1%, p = 0.04). CONCLUSION: Both craniotomy and DC were feasible treatment strategies for acute SDH. The patients with acute SDH and low GCS score treated with craniotomy or DC showed no difference in the outcomes and complications.

The potential of tetrandrine as a protective agent for ischemic stroke.

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

Laparoscopic reduction of intussusception in children by a single surgeon in comparison with open surgery.

The surgical approach for managing intussusception is controversial. In this study, a retrospective analysis of patients undergoing surgical reduction for intussusception over a period of five years was conducted. All patients received either open surgery or laparoscopic approach after failing enema reduction of intussusception. The clinical and operative data were collected and analyzed. Eight patients received open surgery (OPEN group), and 37 patients received laparoscopic surgery, while two (5.4%) of them converted to open surgery. The remaining 35 patients were included in the LAP group. There was no difference in age, gender, clinical symptoms and signs, duration of symptoms, level of intussusception, and complications between the OPEN and LAP groups. In contrast, the operation time and length of hospital stay in the LAP group were significantly shorter than those in the OPEN group (P = 0.013 and P = 0.001 respectively). No recurrence was disclosed in the OPEN group but three patients in the LAP group had recurrent intussusception (8.6%); however, the difference of the recurrence rate between these two groups was not statistically significant (P = 0.40). In conclusion, reducing intussusception with the laparoscopic approach is highly successful and can be performed first for stable patients requiring surgical intervention.

DYT6 Dystonia Mimicking Adolescent Idiopathic Scoliosis Successfully Treated by Pallidal Stimulation.

PURPOSE: Dystonia type 6 (DYT6) is an autosomal dominant monogenic movement disorder that often involves craniocervical and laryngeal regions, but can in rare circumstance present as trunk dystonia or severe scoliosis. Deep brain stimulation of the globus pallidus internus (GPi-DBS) has yielded favorable results in the treatment of DYT6 patients. This report describes the case of a 14-year-old male adolescent with DYT6 dystonia and severe scoliosis who was successfully treated by GPi DBS. PATIENTS AND METHODS: The diagnosis of DYT6 dystonia was made after excluding other etiologies and was confirmed by next-generation sequencing. The patient underwent bilateral GPi-DBS implantation surgery under general anesthesia. RESULTS: The patient's Burke-Fahn-Marsden Dystonia Rating Scale score was 24 before surgery and decreased to 13.5 at 3 months, 3 at 6 months, and 2 at 12 months after bilateral GPi-DBS, corresponding to a 91% improvement from baseline to 12 months post-surgery. The patient's scoliosis improved significantly within 6 months after DBS. No complications occurred during surgery. CONCLUSION: An adolescent DYT6 patient with dystonia-related severe scoliosis was treated by bilateral GPi-DBS. The patient had an excellent outcome at 12 months after surgery, which prevented him from developing severe spinal deformity and disability. Early diagnosis of dystonia in adolescent patients can lead to timely and effective treatment. The etiology of severe scoliosis in adolescents should be carefully evaluated and differential diagnosis including dystonia should be considered. GPi-DBS in patients with DYT6 dystonia can prevent deformity.

VS-5584, a PI3K/mTOR dual inhibitor, exerts antitumor effects on neuroblastomas in vitro and in vivo.

BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is closely related to oncogenesis. PI3K/mTOR inhibitors are considered capable of counteracting the feedback mechanisms within the pathway. In this study, we investigated the antitumor effects of VS-5584, an orally administered PI3K/mTOR dual inhibitor, on neuroblastomas. METHODS: The effects of VS-5584 on proliferation, cell cycle distribution, and related signaling molecules were examined in neuroblastoma cells using the (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide)-based colorimetric assay, flow cytometry, and western blotting, respectively. Nude mice were subcutaneously inoculated with human neuroblastoma cells, followed by VS-5584 treatment for two weeks. Tumor growth was tracked and tumor tissues were subjected to immunohistochemical investigations. RESULTS: In neuroblastoma cells, VS-5584 significantly inhibited proliferation and induced G0/G1 cell cycle arrest. Additionally, VS-5584 decreased the expression of phospho-S6 kinase 1 (p-S6K1), p-retinoblastoma protein, p-cyclin-dependent kinase 2, and cyclin E1, and increased the expression of p21 and p27 in neuroblastoma cells. In mice, VS-5584 significantly suppressed tumor growth in neuroblastomas and downregulated the expression of p-mTOR and p-S6K1 in tumor tissues. CONCLUSIONS: VS-5584 blocks the PI3K/mTOR pathway, induces a G0/G1 cell cycle arrest, and exerts antitumor effects on neuroblastomas both in vitro and in vivo.

In vivo imaging of neuroblastomas using GD2-targeting graphene quantum dots.

BACKGROUND: Patients with neuroblastoma, a common childhood malignancy, often have poor prognosis. It is mandatory to develop an accurate and efficient diagnostic tool for neuroblastomas, so that the treatment can be started early. Graphene quantum dot (GQD), a nanomaterial, can be used to carry proteins, genetic materials, or drugs. GD2, a disialoganglioside, is a surface antigen expressed on neuroblastoma. This study investigated the in vivo targeting and imaging of neuroblastomas using GD2-targeting GQDs. METHODS: GQDs were synthesized and conjugated with anti-GD2 antibody (anti-GD2/GQDs). In vitro cytotoxicity of GQDs and anti-GD2/GQDs was studied in human neuroblastoma cells by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide)-based colorimetric assay. The tumor tracking and imaging of anti-GD2/GQDs in mice were investigated by in vivo imaging system (IVIS). RESULTS: Treatment with GQDs or anti-GD2/GQDs induced no or mild cytotoxicity in fibroblasts and neuroblastoma cells. After co-incubation, GQDs and anti-GD2/GQDs were located in the cytoplasm and nucleus of neuroblastoma cells, with GQDs showing a blue fluorescence and anti-GD2/GQDs an orange/red emission. The IVIS images demonstrated accumulation of the fluorescence of anti-GD2/GQDs in the subcutaneous tumors in mice 24 h after intravenous injection of anti-GD2/GQDs. CONCLUSIONS: Anti-GD2/GQDs may potentially be used for the targeting and imaging of neuroblastomas in vivo.

Tetrandrine attenuates dendritic cell-mediated alloimmune responses and prolongs graft survival in mice.

Tetrandrine, a bisbenzylisoquinoline alkaloid, has significant immunosuppressive effects; however, the effects of tetrandrine on dendritic cells (DCs) and the associated immune reactions are unclear. In this study, we investigated the effects of tetrandrine on DCs and the effects of the tetrandrine-treated DCs on alloimmune reactions in vitro and graft survival in vivo. Tetrandrine significantly downregulated the expression of CD80 and CD86 of DCs and increased their secretion of IL-10 (p = 0.0001). Mixed leukocyte reaction showed that tetrandrine inhibited dendritic-cell allo-stimulatory activity, which was reversed by the anti-IL-10 treatment. An in vivo study demonstrated that tetrandrine-treated DCs prolonged the survival time of skin grafts in mice compared to control (p = 0.005) and decreased cellular infiltration of the graft in the histopathological study. The data suggest that tetrandrine-treated DCs cause immunosuppression and protect skin grafts from rejection. The tetrandrine-induced immunosuppression seems to be partially due to increased IL-10 secretion.