Human neural stem cells.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications.

Endostatin 33 Peptide Is a Deintegrin α6ß1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is the leading cause of death in men and has poor therapeutic outcomes. METHODS: A novel endostatin 33 peptide was synthesized by adding a specific QRD sequence on the basis of the endostatin 30 peptide (PEP06) with antitumor activity. Then, bioinformatic analysis and subsequent experiments were performed to validate the antitumor function of this endostatin 33 peptide. RESULTS: We found that the 33 polypeptides significantly inhibited growth, invasion and metastasis and promoted the apoptosis of PCa in vivo or vitro, which is more significant than PEP06 under the same conditions. According to 489 cases from the TCGA data portal, the α6ß1 high expression group was closely associated with the poor prognosis (Gleason score, pathological N stage, etc.) of PCa and was mainly enriched in the PI3K-Akt pathway. Subsequently, we demonstrated that endostatin 33 peptide can down-regulate the PI3K-Akt pathway via the targeted inhibition of α6ß1, thereby inhibiting the epithelial-mesenchymal transition and matrix metalloproteinase in C42 cell lines. CONCLUSION: The endostatin 33 peptide can exert antitumor effects by inhibiting the PI3K-Akt pathway, especially in tumors with a high expression of the integrin α6ß1 subtype, such as prostate cancer. Therefore, our study will provide a new method and theoretical basis for the treatment of prostate cancer.

Mechanism Study on Chinese Medicine in Treatment of Nodular Goiter.

Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.

Tubeimoside-1: A review of its antitumor effects, pharmacokinetics, toxicity, and targeting preparations.

Tubeimoside-1 (TBMS-1), a natural triterpenoid saponin found in traditional Chinese herbal medicine Bolbostemmatis Rhizoma, is present in numerous Chinese medicine preparations. This review aims to comprehensively describe the pharmacology, pharmacokinetics, toxicity and targeting preparations of TBMS-1, as well the therapeutic potential for cancer treatement. Information concerning TBMS-1 was systematically collected from the authoritative internet database of PubMed, Web of Science, and China National Knowledge Infrastructure applying a combination of keywords involving "tumor," "pharmacokinetics," "toxicology," and targeting preparations. New evidence shows that TBMS-1 possesses a remarkable inhibitory effect on the tumors of the respiratory system, digestive system, nervous system, genital system as well as other systems in vivo and in vitro. Pharmacokinetic studies reveal that TBMS-1 is extensively distributed in various tissues and prone to degradation by the gastrointestinal tract after oral administration, causing a decrease in bioavailability. Meanwhile, several lines of evidence have shown that TBMS-1 may cause adverse and toxic effects at high doses. The development of liver-targeting and lung-targeting preparations can reduce the toxic effect of TBMS-1 and increase its efficacy. In summary, TBMS-1 can effectively control tumor treatment. However, additional research is necessary to investigate in vivo antitumor effects and the pharmacokinetics of TBMS-1. In addition, to reduce the toxicity of TBMS-1, future research should aim to modify its structure, formulate targeting preparations or combinations with other drugs.

Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects.

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent µ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

Antiallodynic Effects of Endomorphin-1 and Endomorphin-2 in the Spared Nerve Injury Model of Neuropathic Pain in Mice.

BACKGROUND: The spared nerve injury (SNI) model is a new animal model that can mimic several characteristics of clinical neuropathic pain. Opioids are recommended as treatment of neuropathic pain. Therefore, the present study was conducted to investigate the antinociceptive effects of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given centrally and peripherally in the SNI model of neuropathic pain in mice. METHODS: The SNI model was made in mice by sparing the sural nerve intact, when the other 2 of 3 terminal branches of the sciatic nerve (common peroneal and tibial nerves) were tightly ligated and cut. Von Frey monofilaments were used to measure the SNI-induced mechanical allodynia-like behavior. The antiallodynic effects of EM-1 and EM-2 were determined after central and peripheral administration in the SNI model of neuropathic pain. Also, the specific opioid receptor antagonists were used to determine the opioid mechanisms of EMs involved in neuropathic pain. Values were expressed as the mean ± standard deviation. RESULTS: Our results showed that the SNI mice developed prolonged mechanical allodynia-like behavior in ipsilateral paw after surgery, with the withdrawal threshold value being 0.061 ± 0.02 g after 14 days. EM-1 and EM-2 produced significant antiallodynic effects in ipsilateral paw after intracerebroventricular (i.c.v.) administration, more effective than that of morphine. The peak withdrawal thresholds of 10 nmol EM-1 and EM-2 determined at 5 minutes after injection were 0.92 ± 0.36 and 0.87 ± 0.33 g, respectively, higher than that of morphine (0.46 ± 0.20 g). Moreover, both EMs (10 nmol, i.c.v.) exerted significant antiallodynic effects in the contralateral paw, whereas no significant antinociceptive activity was seen after i.c.v. administration of morphine with equimolar dose. It was noteworthy that EM-1 and EM-2 produced antinociception through distinct µ1- and µ2-opioid receptor subtypes, and the EM-2-induced antiallodynia contained an additional component that was mediated by the release of endogenous dynorphin A, acting on κ-opioid receptor. In addition, the antiallodynic activities of peripheral administration of EM-1, EM-2, and morphine were also investigated. Intraplantar, but not subcutaneous administration of EM-1 and EM-2 also exhibited potent antinociception, establishing the peripheral and local effects. Both µ1- and µ2-opioid receptor subtypes, but not the δ- or κ-opioid receptors were involved in the peripheral antiallodynia of EMs. CONCLUSIONS: The present investigation demonstrated that both EM-1 and EM-2 given centrally and peripherally produced potent antiallodynic activities in SNI mice, and differential opioid mechanisms were involved.

Physiological characteristics, dry matter, and active component accumulation patterns of Changium smyrnioides in response to a light intensity gradient.

CONTEXT: Changium smyrnioides Wolff (Apiaceae) is an endangered medicinal plant with numerous pharmacological uses. OBJECTIVE: To investigate the effect of light intensity levels on the growth and accumulation of secondary metabolites of C. smyrnioides, cultivated seedlings were subjected to different relative light intensities via sun-shading. MATERIALS AND METHODS: Changium smyrnioides seedlings were subjected to five irradiance treatments (100, 60.54, 44.84, 31.39, and 10.56% sunlight) in glasshouse for 9 months. Enzymatic and non-enzymatic antioxidants with spectrophotometric method, photosynthetic parameters with Li-6400XT, dry matter accumulation and active component contents in the root with spectrophotometric and HPLC method were analyzed. RESULTS: With an increase in relative light intensity levels, activities of enzymatic and non-enzymatic antioxidants, and malondialdehyde (MDA) contents were increased overall, while net photosynthetic rate (Pn) and dry matter accumulation patter first increased and then declined. The highest net photosynthetic rate (30.68 µmol/m2·s) and dry root weight (5.07 g) were achieved under 60.54% sunlight. Lower relative light intensity levels stimulated the accumulation levels of bioactive compounds in the roots so that the highest contents of mannitol (1.35%) and choline (405.58 µg/g) were recorded under 31.39% sunlight, and the highest polysaccharide content (10.80%) were achieved under 44.84% sunlight. With a decrease in the relative light intensity levels, the water-soluble component content increased first and then decreased. DISCUSSION AND CONCLUSION: The results revealed that 31.39-60.54% sunlight serve as appropriate relative light intensity conditions for cultivated C. smyrnioides.

Long-term follow-up and management of prenatally detected, isolated hydronephrosis.

PURPOSE: The aim of the study was to determine the outcome and management of infants with isolated hydronephrosis, detected prenatally and confirmed postnatally. MATERIALS AND METHODS: Between January 1988 and January 2008, the files of 629 children (492 males and 137 females), who were diagnosed prenatally with isolated, unilateral hydronephrosis, and the diagnosis was confirmed postnatally, were retrospectively reviewed. The median follow-up time was 142 months. Serial ultrasonography and isotope diuretic renography nuclear imaging were performed. Hydronephrosis was assessed and classified according to the Society of Fetal Urology (SFU) grading system. RESULTS: Initially, all of the children were treated conservatively. Stabilization occurred in all children with grade 1 hydronephrosis, in 87% of children (144) with grade 2 hydronephrosis, and in 30% of children (37) with grade 3 hydronephrosis. However, 13% of children (21) with grade 2 hydronephrosis, 70% of children (85) with grade 3 hydronephrosis, and 100% of children with grade 4 hydronephrosis received surgical intervention according to our predetermined criteria. Ninety-five patients (late pyeloplasty group) were treated for a reduction for a differential renal function (DRF) to less than 40%, and 80 children (early pyeloplasty group) underwent surgery for a DRF more than 40%, but hydronephrosis progressed to higher grades or failed to improve and had poor radiotracer clearance. Significant improvements after pyeloplasty were noted in both groups with respect to the DRF and the ratio of the depth of the calyces to the thickness of the parenchyma (C/P ratio; P < .0001). The improvement in DRF was greater in the late pyeloplasty group than the early pyeloplasty group (P = .044), whereas the improvement in the C/P ratio was greater in the early pyeloplasty group than the late pyeloplasty group (P = .001). The ipsilateral DRF was preserved in the early pyeloplasty group, whereas the ipsilateral DRF was still less than 40% in the late pyeloplasty group. The improvement in DRF was significant during the first year postoperatively and became stable thereafter. The C/P ratio was inversely correlated with the DRF in the patients before and after pyeloplasty (r = -0.257; P = .01; and r = -0.616; P = .001, respectively). CONCLUSIONS: All infants with SFU-1 and most infants with SFU-2 hydronephrosis have relatively benign conditions and do not need an invasive procedure. Although greater improvement occurred in patients with an initial DRF less than 40%, the reduced DRF did not recover to the predeterioration level postoperatively. Earlier surgical intervention after a short period of strict clinical surveillance is beneficial for preserving renal function for patients with persistent SFU-3 or SFU-4 hydronephrosis.

Lymphangioma of bladder.

Lymphangioma in the bladder is extremely rare. An 8-year-old girl presented with a terminal hematuria associated with intermitted fever. Ultrasonography, computed tomogram, and retrograde urethrography showed a mass that was in the wall of the bladder. The tumor was red and found to be bulging into the bladder on the right lateral wall of the bladder by cystoscopy. A partial cystectomy was performed and histology revealed a lymphangioma of the bladder. The patient was followed up for 3 years with no evidence of recurrence. This case, to the authors' knowledge, represents the third reported case of lymphangioma of bladder.Lymphangiomas are benign, soft-tissue tumors of lymphatic origin. They rarely affect the urinary system and a location in the bladder is extremely rare. Only 2 cases of lymphangioma of the bladder have been reported worldwide since 1983. The present report describes a patient with a lymphangioma of the bladder and the imaging characteristics of the lesion are reported, including imagings of sonography, computed tomography, retrograde urethrography, and histologic examination.

[Optimization of extracting method and inhibitory action of recombinant human endostatin in bladder cancer].

OBJECTIVE: To explore the optimal method for protein expression in rhES (recombinant human endostatin) and study the anti-tumor activities of rhES in solid tumor and established cell line. METHODS: Different IPTG concentrations, the timing of adding IPTG into the culture medium and the different time of expression were employed to explore the optimized conditions of protein expression. Activity examination: (1) animal experiment: nude mice bearing subcutaneous cancer in treated group and controlled group were observed. (2) cellular experiment: the inhibitory effect of rhES in T-24 established cell line were observed by MTT assay and cancer cell growth curve. RESULTS: The expression of rhES protein was 58.65%. Of all the E. coli body proteins, the protein purity after purification was 96.22%. Activity examination indicated that rhES could inhibit the growth of solid tumor and the established cell line. In animal experiment, the tumor inhibition rate was 66.8%. Cell experiment: the 50% inhibitory concentration (IC(50)) was 22 microg/ml. The cell population decreased 58.75% than the control group at Day 7 in the tumor cell growth curve. CONCLUSION: A high expression and activity of rhES protein can be obtained by the optimized expression conditions. rhES can inhibit the cellular growth in both solid tumor and established cell line of bladder cancer.

[Expression of Stat3, HIF-1alpha and VEGF in Wilms' tumor].

OBJECTIVE: To study the expression of signal transducer and activator of transcription 3 (Stat3), hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in Wilms' tumor and their roles in the development of Wilms' tumor. METHODS: The expression of Stat3, HIF-1alpha and VEGF were detected by the immunohistochemical staining in 52 specimens from Wilms' tumor tissues, 47 from adjacent kidney tissues and 8 from normal kidney tissues. The expression intensity was analyzed by computer image processing. RESULTS: The expression of Stat3, HIF-1 and VEGF were significantly up-regulated in Wilms' tumor tissues compared to those in adjacent tissues and normal kidney tissues (P < 0.05). Stat3 and VEGF proteins in Wilms' tumor tissues of stage III-IV and high risk histopathology were significantly higher than those of stage I-II and low risk histopathology. The higher expression of HIF-1 in Wilms' tumor tissues was shown in tumors with high risk histopathology and tumor size > or = 6 cm. CONCLUSIONS: Increased expression of Stat3, HIF-1 and VEGF were found in Wilms' tumor tissues, and may be related to the development and angiogenesis of Wilms' tumor. Stat3 may regulate the expression of HIF-1 and VEGF, so it could be an effective target for inhibiting VEGF expression and angiogenesis of Wilms' tumor.

Ureteral polyps: an etiological factor of hydronephrosis in children that should not be ignored.

To better define the demographics, urothelial distribution and typical gross anatomic and radiologic appearances of fibroepithelial polyps of the ureter in children. We reviewed 15 cases of fibroepithelial polyps of the ureter with hydronephrosis from the archives of our department. Data were collected from radiographic studies, gross anatomic pathology and pathology and radiology reports and categorized by age, sex, clinical presentation, lesion size and location. The mean patient age was 9.1 years, and 80% were male. All of them presented with hematuria and/or flank pain. The polyps were located in the upper ureter or ureteropelvic junction (UPJ) and pelvis. Of the polyps, 60% were multiple polyps or filiform, and 40% were single or bilobed and 1-6 cm in size. Only four cases showed typical filling defect on intravenous urography. In five cases, sonography showed a mildly echogenic structure extending into the ureter from the renal pelvis. Enhanced CT revealed soft tissue filling UPJ or/and proximal ureter in six cases, and hydroureter was found in one case by three-dimensional (3D) image. Fibroepithelial polyps were diagnosed in all cases by postoperative histological examination. Fibroepithelial polyps are the most common benign tumors of the ureter. Congenital factor may be associated with the origin of fibroepithelial polyps in children. The preoperative diagnosis of ureteral polyps is difficult. A history of flank pain, hematuria or both, other than abdominal mass, light-to-moderate hydronephrosis with soft-tissue in UPJ or upper ureter, shown by sonography and radiological examination, may help in the diagnosis of ureteral polyps in children. Ureteral polyps should be recognized as an important etiology for hydronephrosis in children.

In vitro and in vivo characterization of opioid activities of endomorphins analogs with novel constrained C-terminus: evidence for the important role of proper spatial disposition of the third aromatic ring.

In the present study, the C-terminus of endomorphin (Tyr(1)-Pro(2)-Trp/Phe(3)-Phe(4)-NH(2), EMs) analogs [Xaa(4)-R]EMs, modified by substitution of a non-aromatic residue for Phe(4) and ending up with -NH-benzyl, were designed to generate an atypical conformationally constrained peptide set. We investigated the effects of these analogs on the opioid receptors affinity, guinea pig ileum (GPI) and mouse vas deferens (MVD) activity, system arterial pressure (SAP), heart rate (HR), antinociception and colonic motility. Analogs 5 ([D-V(4)-Bzl]EM1) and 10 ([D-V(4)-Bzl]EM2), which exhibit appropriate spatial orientations of the third aromatic ring, were about 3-4 times more potent than their parents both in vivo and in vitro. However, a drastic loss of activity was found in analogs 2 ([A(4)-Bzl]EM1) and 7 ([A(4)-Bzl]EM2), which possess improper spatial orientations of the third aromatic ring. Interestingly, analog 7 or 3 ([G(4)-Bzl]EM1), when injected intravenously (i.v.), produced significantly different changes in SAP from their parents. Surprisingly, analog 4 displayed relatively higher vasodepressor activity but significantly less potent colonic contractile activity than analog 5. This may be elicited by the differences in the spatial disposition of the third aromatic ring, which were verified by molecular modeling. Our results indicate that the proper spatial disposition of the third aromatic ring plays an important role in the regulation of pharmacological activities of EMs.

The expression of HSP70 and HSP90alpha in children with Wilms tumor.

BACKGROUND/PURPOSE: Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. Some studies also showed that they might predict clinical prognosis. The aim of this study is to detect the expression of HSP70 and HSP90alpha in children with Wilms tumor and explore its clinical significance. METHODS: The expression of HSP70 and HSP90alpha was evaluated in the tissue specimens of 30 patients (13 males and 17 females aged 5 months to 9 years with mean age of 37.4 +/- 23.9 months) with Wilms tumor by histochemistry and reverse transcriptase polymerase chain reaction techniques. According to the NWTS3 study criteria, all patients were favorable histological types, including mesenchymal type in 6, blastemal type in 12, and epithelium type in 7, and mixed type in 5. The clinical staging of the tumor included stage I in 4, stage II in 8, stage III in 12, and stage IV in 6. RESULTS: On the reverse transcriptase polymerase chain reaction study, the amount of HSP70 and HSP90alpha mRNA in the tumor tissue was lower than in the controls. The HSP70 to beta-actin ratio was 0.74 +/- 0.14 and 1.38 +/- 0.22 in the tumor tissue and the normal kidney, respectively (P < .0001). The HSP90alpha to beta-actin ratio was 0.60 +/- 0.14 and 0.96 +/- 0.15 in the tumor tissue and the normal kidney, respectively (P < .0001). On immunolabeling, the expression of HSP70 and HSP90alpha was confined to blastemal and epithelial components, whereas the tumor stroma was negative. The expression of HSP70 and HSP90alpha was mainly located in the cytoplasm of the tubular epithelial cell, mesangial cell, and endothelial cell in the normal kidney. The positive expression rates of HSP70 and HSP90alpha proteins were significantly lower in the tumor group (73.3%, 22/30; 76.7%, 23/30) than in the control group (100%, 30/30; 100%, 30/30), P = .002 and P = 0.005, respectively. Positive correlation was found between HSP70 gene and protein expression (r = 0.64, P < .0001). Positive correlation was also found between HSP90alpha gene and protein expression (r = 0.67, P < .0001). HSP70 and HSP90alpha gene and protein expression showed no correlation with its corresponding tumor stages (P > .05). The expression of HSP70 and HSP90alpha genes was significantly higher in children who survived when compared with those patients who died during the follow-up period, P = .017 and P = 0.004, respectively. The positive expression rates of HSP70 and HSP90alpha proteins were also significantly higher in children who survived (82.6%, 19/23; 87.0%, 20/23) than in those who died (42.9%, 3/7; 42.9%, 3/7), P = .037 and P = 0.016, respectively. CONCLUSIONS: The expression of HSP70 and HSP90alpha decreased in Wilms tumor and is confined to blastemal and epithelial components; it was higher in patients who survived, which suggested that they might be of prognostic value.

Postoperative intussusception in children: a review of 14 cases.

OBJECTIVE: To search the etiologic factor, clinical diagnosis points and treatment of postoperative intussusception (PI). METHODS: To retrospectively review the clinical materials of 14 cases with PI including the cause of disease and treatment. RESULTS: PI occurred within 10 days (average 4 days) after the primary operation. Bowel obstructive symptoms gradually emerged. One case was diagnosed with intussusception by sonography and received enema reduction of intussusception by hydrostatic pressure. Thirteen cases were performed secondary operation. Small intestine was main site of intussusception. Manual reduction of the lesion was performed in 12 cases and bowel resection and anastomosis was done in 1 case with bowel necrosis. CONCLUSION: PI should be suspected if child presents with the symptoms of ileus in early postoperative period. Abdominal sonography may have some value on diagnosis of PI. Operation is the first choice for the treatment of PI.