KIF18B: an important role in signaling pathways and a potential resistant target in tumor development.

KIF18B is a key member of the kinesin-8 family, involved in regulating various physiological processes such as microtubule length, spindle assembly, and chromosome alignment. This article briefly introduces the structure and physiological functions of KIF18B, examines its role in malignant tumors, and the associated carcinogenic signaling pathways such as PI3K/AKT, Wnt/ß-catenin, and mTOR pathways. Research indicates that the upregulation of KIF18B enhances tumor malignancy and resistance to radiotherapy and chemotherapy. KIF18B could become a new target for anticancer drugs, offering significant potential for the treatment of malignant tumors and reducing chemotherapy resistance.

Case report: Sarcomatoid renal cell carcinoma masquerading as hydronephrosis.

Sarcomatoid renal cell carcinoma (SRCC), a manifestation of sarcomatoid dedifferentiation in renal cell carcinoma, is characterized by elevated invasiveness and a grim prognosis. Typically, SRCC patients present with advanced or metastatic conditions and survival rates rarely extend beyond one year. In this study, we describe a case of SRCC characterized by the patient exhibiting right flank pain without hematuria. Initially, imaging interpretations led to a diagnosis of severe hydronephrosis. Subsequently, an open right nephrectomy post-surgery confirmed the pathology of sarcomatoid renal cell carcinoma.

SPRY1 Deficiency in Keratinocytes Induces Follicular Melanocyte Stem Cell Migration to the Epidermis through p53/Stem Cell Factor/C-KIT Signaling.

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes (KCs). KCs and melanocytes respond to UV exposure by eliciting a tanning response. However, how KCs and melanocytes interact in the absence of UV exposure is unknown. In this study, we demonstrate that after SPRY1 knockout in epidermal KCs, melanocyte stem cells in the hair follicle exit the niche without depleting the pool of these cells. We also found that melanocyte stem cells migrate to the epidermis in a p53/stem cell factor/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal KCs. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of melanocyte stem cells to the epidermis is due to loss of SPRY1 in epidermal KCs and show the potential for developing therapies for skin pigmentation disorders by manipulating melanocyte stem cells.

Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.

BACKGROUND: Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. METHODS: The present study used the differentially expressed genes (DEGs) obtained from the "Limma" package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified-claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)-by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. RESULTS: The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. CONCLUSION: IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.

Glycyl-tRNA Synthetase Induces Psoriasis-Like Skin by Facilitating Skin Inflammation and Vascular Endothelial Cell Angiogenesis.

Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA synthetases are universally expressed enzymes that catalyze the first step of protein synthesis. Glycyl-tRNA synthetase (GARS) is a member of the aminoacyl-tRNA synthetase family. In addition to its canonical function, we found that GARS was overexpressed in the serum and skin lesions of patients with psoriasis. Moreover, GARS was highly expressed in human skin keratinocytes, and GARS knockdown in keratinocytes suppressed cell proliferation and promoted apoptosis through NF-κB/MAPK signaling pathway. Moreover, intradermal injection of recombinant GARS protein caused skin thickening, angiogenesis, and IFN/TNF-driven skin inflammation. Intriguingly, the reported functional receptor for GARS, cadherin 6 (CDH6), was specifically expressed in vascular endothelial cells, and we found that keratinocyte-derived GARS promotes inflammation and angiogenesis of vascular endothelial cells through CDH6. In addition, intradermal injection of GARS aggravated the phenotype and angiogenesis in imiquimod-induced psoriasiform dermatitis models, whereas the psoriatic phenotype and angiogenesis were relieved after knockdown of GARS by adeno-associated virus. Taken together, the results of this study identify the critical role of GARS in the pathogenesis of psoriasis and suggest that blocking GARS may be a therapeutic approach for alleviating psoriasis.

Case Report: A testicular torsion as an initial presentation of a patient with metastatic cecum signet-ring cell cancer.

Secondary neoplasms of the testes from solid tumors are rare and usually present as a painless mass. Metastatic cecum signet-ring cell cancer of the testis is extremely rare. The orchioncus usually shows hypervascularity on color Doppler ultrasound. The present study reports an unusual case of testicular secondary signet-ring cell carcinoma mimicking missed testicular torsion in a 55-year-old male patient with right scrotal swelling and intermittent pain for 10 days. As color Doppler ultrasound showed an avascular distribution of the enlarged right testis, missed testicular torsion was initially diagnosed. Right-sided orchiectomy was performed, and pathology of the resected testis revealed an intestinal-type adenocarcinoma with mucinous and signet-ring cell features. This pathological feature led to further endoscopic colorectal biopsy of the digestive tract, which revealed poorly differentiated adenocarcinoma of the cecum with signet ring cell features similar to those of testicular specimens. In conclusion, differential diagnosis should be considered for rare testicular neoplasms, as was seen in this rare occurrence of testicular torsion in a patient who initially presented with metastatic colorectal cancer. A correct preoperative diagnosis can change the management and outcome. This report shares our reasons for misdiagnosis and opinions on diagnosing and treating this kind of case.

UBE2L3 Reduces TRIM21 Expression and IL-1ß Secretion in Epidermal Keratinocytes and Improves Psoriasis-Like Skin.

Proinflammatory cytokines, such as IL-1ß, are important mediators of psoriasis. UBE2L3, an E2 enzyme, is thought to be an indirect target of IL-1ß secretion by binding to ubiquitin ligases such as TRIM21. However, its role in psoriasis remains unknown. In this study, we found that UBE2L3 expression was decreased in psoriatic epidermis, whereas caspase 1 and IL-1ß signaling were strongly activated. When normal human epidermal keratinocytes were stimulated with nigericin, adenosine triphosphate, and poly(dA:dT), downregulation of UBE2L3 and increased secretion of IL-1ß were observed. Treatment with a caspase 1 inhibitor reversed the decrease in the level of UBE2L3. In addition, UBE2L3 overexpression reduced TRIM21, decreased signal transducer and activator of transcription 3 pathway activity, and reduced the level of the IL-1ß precursor (pro‒IL-1ß). Consistently, silencing UBE2L3 enhanced TRIM21 expression, signal transducer and activator of transcription 3 activation, and pro‒IL-1ß production. Finally, in an imiquimod-induced mouse model, UBE2L3 reduction and caspase 1 activation were localized in the epidermis, whereas overexpression of UBE2L3 ameliorated psoriasis-like lesions and reduced pro‒IL-1ß and mature IL-1ß levels in the epidermis. Thus, UBE2L3 may be a protective biomarker that regulates IL-1ß and inhibits TRIM21 in the epidermis of psoriasis.

Mupirocin blocks imiquimod-induced psoriasis-like skin lesion by inhibiting epidermal isoleucyl-tRNA synthetase.

BACKGROUND: The Isoleucyl-tRNA synthetase (IARS) catalyzes isoleucine to the corresponding tRNA, maintaining the accuracy of gene translation. Its role in psoriasis has been not investigated so far. In this study, we aimed to investigate the mechanisms underlying the efficacy of IARS inhibitor, mupirocin, treatment for psoriasis. METHODS: The expression of IARS was determined by immunofluorescence, Western blot and qRT-PCR in normal healthy control- and psoriatic human skin. An imiquimod (IMQ) -induced psoriasis-like skin disease model was used to study the phenotypes changed by an IARS inhibitor, mupirocin (MUP). Endotypes were analyzed by RNA-seq, R&D Luminex multi-factor technique, ELISA, immunofluorescence and flow cytometry. Additionally, the effect of MUP on epidermal keratinocytes (KCs) were conducted in-vitro in primary cultured human KCs. RESULTS: We found the expression of IARS was higher in psoriatic skin than in healthy controls. In IMQ-induced psoriasis-like C57BL/6 J mouse model, MUP reversed IMQ-induced keratinocytes proliferation, expression of inflammatory cytokines and infiltration of immune cells. Furthermore, in cultured human keratinocytes, MUP inhibited proliferation, but promoted apoptosis, which may be related with STAT3 signaling pathway. CONCLUSION: Our finding of blocking the infiltration of immune cells by inhibiting the formation of IARS, could be one mechanism to explain the effect of MUP in the treatment of psoriasis. Developing strategies targeting suppression IARS should open new perspectives for the treatment of psoriasis. Video Abstract.

Rare Primary Adrenal Tumor: A Case Report of Teratomas and Literatures Review.

Teratomas are very rare, originating from embryonal germ layers. The majority of them are mature, most common in the gonads, and with only 15% out of gonads. In particular, primary adrenal teratomas are extremely rare. The present study reported a case of a young female patient with right adrenal tumor who underwent intermittent pain in the right waist and abdomen and whose CT of adrenal gland showed an 88 mm × 79 mm × 69 mm mass. Besides, her adrenal gland-related hormones are not abnormal. Laparoscopic adrenal tumor resection was performed on her and the histopathological results confirmed that the mass was mature adrenal teratomas. As a newly diagnosed case, strict and regular follow-up is needed, and it is also necessary to detect her AFP and check her adrenal CT in the future. In addition, we have reviewed the literature from 1952 to the present, and a total of 49 cases of adrenal teratoma have been identified and analyzed.

Comparison of stone dusting efficiency when using different energy settings of Holmium: YAG laser for flexible ureteroscopic lithotripsy in the treatment of upper urinary tract calculi.

PURPOSE: The aim of this study is to evaluate the impact of different pulse energy settings on dusting efficiency in flexible ureteroscopic lithotripsy (fURSL) for the treatment of upper urinary tract calculi. MATERIALS AND METHODS: Data of 88 consecutive patients who underwent fURSL for upper urinary tract calculi by a single surgeon in our department From August 2017 to August 2018 were reviewed retrospectively. Lumenis Power Suite 100W lithotripter with a 200 ?m laser fiber was used to comminute stones. According to energy settings, patients were divided into three groups- low energy group (LE: 0.3-0.6J), middle energy group (ME: 0.7-1.0J), high energy group (HE: 1.1-1.5J). Frequency was set at 30Hz in all patients. ANOVA and Chi square tests were applied to compare the difference of the mean lithotripsy and operation time, early stone-free rate (eSFR), overall stone-free rate (oSFR) and complication rate. RESULTS: A total of 32, 36 and 20 patients were included in the LE, ME and HE groups, respectively. There was no difference in the age, gender distribution or in any other stone characteristics among the three groups. The mean lithotripsy time of LE, ME, HE was 10.9±7.6, 16.1±7.0, 23.0±15.0 min respectively. The mean operation time of the three groups was 16.9±7.7, 22.3±7.1, 29.2±14.9 min respectively. There were significant differences on the mean lithotripsy time (P=0.002) and the mean operation time (P=0.001) among the three groups. The stone-free rate was 31.8% and 87.5% respectively in eSFR and oSFR. No statistical significance was detected among the three groups in terms of the eSFR (P=0.89), oSFR (P=0.86), and complication rate (P=0.97). CONCLUSION: In fURSL with dusting, low energy (0.3-0.6J) is more efficient than middle (0.7-1.0J) and high energy (1.1-1.5J). As energy increased, dusting efficiency decreased dramatically. Consequently, we recommend low pulse energy (0.3-0.6J) as the optimal dusting strategy for fURSL.

[ASL-based Observation of Central Nervous System Responses to Acupuncture Analgesia for People with Different Sensitivities].

OBJECTIVE: To examine the effects of different sensitivities on the effectiveness of acupuncture analgesia by observing activation change characteristics of cerebral areas resulting from the influences of constitutions on analgesia effects and to discuss the response mechanism of central nervous system (CNS) to determine the factor of constitutions on acupuncture efficacy using cerebral functional magnetic resonance imaging arterial spin labeling (fMRI-ASL). METHODS: Participants with different sensitivities were assessed according to standard screening and grouped into two groups: insensitivity group (n＝24) and sensitivity group (n＝22). All participants were given acupuncture at the left-sided Zusanli point. Pressure pain threshold (PPT) of their body surface was determined before and after the acupuncture, and the two groups were subsequently compared in terms of analgesic effects and PPT rate of change; cerebral fMRI-ASL was performed; software such as SPM 8 and ASLtbx were utilized to preprocess the results, and correlation between regional cerebral blood flow (rCBF) and visual analog scale (VAS) score was determined using Pearson's correlational analysis. RESULTS: VAS score in the sensitivity group was significantly higher than that in the insensitivity group (P< 0.05); after acupuncture, PPT rate of change in the sensitivity group was higher than that in the insensitivity group (P< 0.05). The analyses revealed that there was a negative correlation between rCBF and VAS score for the right-sided anterior cingulate cortex in the insensitivity group and superior frontal gyrus in the sensitivity group (|r|>0.3 and P<0.05). CONCLUSION: Different sensitivity to acupuncture is one of the crucial factors influencing analgesia effects. The sensitivity group had superior analgesia effect than the insensitivity group. Acupuncture might deactivate cerebral functional areas to generate analgesic effects.The superior frontal gyrus and bilateral anterior cingulate cortex, because of deactivation, play a positive role in sensitive patients, which is probably one of the CNS cerebral areas responding to acupuncture analgesia of people who are sensitive to acupuncture.

Malignant mesothelioma of the tunica vaginalis testis: A case report and literature review.

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor without specific clinical manifestations, mainly including hydrocele formation and a painless mass. We herein present the case of a patient with hydrocele of the left testis, without any other complaints. Tunica vaginalis subinvolution was performed, and postoperative pathological examination revealed a malignant mesothelioma arising from the left tunica vaginalis testis. Whole-body positron emission tomography-computed tomography (PET-CT) and subsequent abdominal and pelvic magnetic resonance imaging (MRI) revealed no evidence of local lymphadenopathy. Radical left orchiectomy was performed after the pathological diagnosis. The pathological examination after the second surgery demonstrated that the tumor had invaded the adjacent periorchium and spermatic cord, but there was no evidence of local lymph node metastasis. Pemetrexed and cisplatin were administered at a dose of 900 and 130 mg, respectively, on the first day of a 28-day cycle. After 6 months of therapy, the disease had not progressed on abdominal and pelvic PET-CT and MRI. The patient was still followed up in our urology outpatient clinic at the time of the present report. Although testicular hydrocele is a common and easily diagnosed condition, detailed medical history and physical examination are required. Thus, when clinicians encounter patients with testicular hydrocele, a variety of possible causes must be considered, including testicular or paratesticular tumors, even rare tumors such as mesothelioma of the tunica vaginalis testis.

[Effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, VEGF and ColX in impaired cartilage of rabbits with knee osteoarthritis].

OBJECTIVE: To investigate the effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, vascular endothelial growth factor (VEGF) and type X collagen (ColX) in impaired cartilage of rabbits with knee osteoarthritis (KOA) and explore its possible mechanisms. METHODS: Forty New Zealand rabbits were randomized equally into normal control group, KOA model group, eletroacupuncture with close-to-bone needling group (CN group), and normal thrust needing group (NTN group). In the latter 3 groups, KOA was induced by Hulth-Telhag treatment and evaluated with X-ray examination, and 6 weeks after the modeling, eletroacupuncture for 20 min was administered in CN and NTN groups at the acupoints "Zusanli", "Waixiyan", "Neixiyan", "Liangqiu" and "Yinlingquan" in the left knee joints once daily for 5 days as a treatment cycle. After 5 treatment cycles, the rabbits were examined for behavioral changes, cartilage morphology, and Mankin scores; The protein and mRNA expressions of S0x9, VEGF, and ColX were examined using Westen blotting, immunohistochemistry, and RT-PCR as appropriate. RESULTS: The rabbits in the model, CN and NTN groups showed significant changes in behaviors and cartilage histomorphology after the modeling and after the treatments. HE staining showed that cartilage injury was repaired and tended to recovery in CN and NTN groups. The cartilage pathologies was severer in the model group than in the normal control, CN and NTN groups (P<0.01); Sox9 protein increased and VEGF mRNA level decreased in CN and NTN groups after treatment as compared with those in the model group (P<0.01). CONCLUSION: Eletroacupuncture with close-to-bone needling can effectively improve KOA in rabbits probably by enhancing Sox9 and reducing VEGF and ColX expressions in the cartilage to inhibit hypertrophic differentiation of the chondrocytes, maintain chondrogenic phenotype and repair cartilage cells.

[Effects of Short Thrust Needing plus Electroacupuncture Intervention on Cartilage Tissue in Rabbits with Knee Osteoarthritis].

OBJECTIVE: To observe the effectiveness of short thrust needling (STN, close-to-bone needing) plus electroacupuncture (EA) in healing knee cartilage tissue and in regulating expressions of cartilage vitamin K dependent gamma-glutamyl carboxylase (GGCX), matrix metalloproteinase-13 (MMP 13) and serum uncarboxylated matrix gla protein (ucMGP) in rabbits with knee osteoarthritis (KOA), so as to reveal its mechanism underlying improvement of KOA. METHODS: Forty New Zealand rabbits were randomly divided into normal, model, EA and STN+ EA groups (n = 10 in each group). The KOA model was created by cutting the medial lateral ligament and medial parapatellar arthrotomy of rabbits as described by Hulth and colleagues. For rabbits in the STN+ EA group, "Neixiyan" (EX-LE 4) and "Waixiyan" (ST 35) were punctured with filiform needles by controlling the needle-tip obliquely to advance till the bone surface of the knee joint cavity, and "Yinlingquan" (SP 9) and "Zusanli" (ST 36) punctured by holding the filiform needles vertically along the tibia, and "Liangqiu" (ST 34) was punctured by controlling the filiform needle to advance till the thigh-bone, followed by EA stimulation. EA (2 Hz/100 Hz, 1-3 mA) was applied to unilateral EX-LE 4 and ST 35, and ST 36 and SP 9, separately for 20 min, once daily for 20 days except weekends. The pathological changes of the knee cartilage cells were observed using H. E. staining, Toluidine blue staining and electron transmission microscope, respectively. The immunoactivity of GGCX of the knee cartilage was determined by immunohistochemistry and the expression levels of GGCX and MMP 13 proteins in the cartilage were detected by Western blot, and the content of serum ucMGP was assayed by ELISA. RESULTS: H. E. staining, Toluidine blue staining and electron transmission microscope results showed that pathological changes of knee cartilage cells in structure after modeling were improved in both the STN+ EA and EA groups, particularly the former group. In comparison with the normal group, the expression levels of GGCX protein in the cartilage tissue showed by both Western blot and immunohistochemistry were notably down-regulated (P<0.01), and the cartilage MMP 13 protein expression and serum ucMGP content were considerably up-regulated in the model group (P<0.01, P<0.05). After STN+ EA and simple EA, the decreased GGCX and the increased MMP 13 expression and serum ucMGP content were reversed (P<0.01, P<0.05). The effects of STN+EA were significantly superior to those of simple EA in down-regulating MMP13 and ucGLA levels, and upre-gulating GGCX expression. CONCLUSION: Both STN+ EA and simple EA can effectively improve pathological changes of cartilage cells in KOA rabbits, which may be associated with their actions in up-regulating the expression of cartilage GGCX protein and lowering the levels of serum ucMGP content and cartilage MMP 13 protein expression, and the effects of STN+ EA are better.

[Characteristics of Deqi Induced by Needling Zusanli (ST 36) in 527 Healthy Volunteers with Different Constitutions].

OBJECTIVE: To explore the relationship between the theory of constitution in terms of Chinese medicine and clinical efficacy of acupuncture treatment via analyzling the characteristics of Deqi during acupuncture stimulation of Zusanli (ST 36) in healthy volunteers with different constitutions. METHODS: In the present study, a total of 527 healthy undergraduate student volunteers (267 girls and 260 boys) were recruited. They received questionnaire first about their constitutions in accordance with Professor WANG Qi's Classification and Determination of Constitution in terms of Chinese medicine. Then, the subjects were asked to take a supine position on a check-bed, a qualified acupuncturist held a sterilized fifiform needle to rapidly insert it into ST 36 and manipulated the acupuncture needle with uniform reinforcing-reducing technique at a frequency of about 60-90 times/min and an amplitude of 0.3-0.5 cm. The status of Deqi was assessed by using visual analogue scale (VAS). RESULTS: Needling sensations mainly involve soreness, numbness, heaviness, distension, dull pain and propagated sensations along meridian (PSC). During acupuncture stimulation, most subjects experienced distension sensation, accounting for 90.3%, followed by soreness, accounting for 45.9%. Except for PSC reaction, the rest 5 needling sensations had no statistical difference in their occurrence rates in those subjects with different constitutions (P>0.05). The PSC appeared a higher incidence in yin-yang harmony(balanced) constitution subjects than in qi- deficiency, yang-deficiency, blood-stagnation and qi-stagnation constitution subjects (P<0.05). The intensity of soreness was obviously stronger in the balanced constitution subjects than in qi-deficiency, yang-deficiency, yin-deficiency, phlegm-damp, damp-heat and qi-stagnation constitution subjects (P<0.05), while the intensity of distension sensation was apparently stronger in the balanced constitution subjects than in simpleyang-deficiency subjects (P<0.05). CONCLUSIONS: Except for PSC, the Deqi sensations of soreness, numbness, heaviness, distension and dull pain induced by acupuncture stimulation of ST 36 are comparable in the occurrence rates in healthy volunteer subjectswith different (9 types of) constitutions in terms of Chinese medicine, whereas the intensity of soreness may be the important factor for acupuncture induced pain relief. A certain correlation between the constitution and acupuncture effectiveness exists, suggesting that acupuncture treatment should vary from patient to patientin clinical practice.

[Effect of Electroacupuncture with Near-to-bone Needling to Chondrocyte Apoptosis and Proliferation on the Knee Osteoarthritis Model].

OBJECTIVES: To study the effect of electroacupuncture with near-to-bone needling on the proliferation and apoptosis of knee osteoarthritis. METHODS: Totally 40 New Zealand rabbits were randomly divided into two groups, the normal group (A, n =10) and the modeling group (n =30). Hulth-Telhag method was applied 30 rabbits to establish rabbit left knee osteoarthritis model, and evaluated by X-ray after 6 weeks. Then divided the 30 modeling rabbits into electroacupuncture with near-to-bone needling group (C,n =10), electroacupuncture with ordinary needling group (D,n =10) and model group (B ,n =10) randomly. Four treatments (5 d as one course of treatment) were applied to C group and D group, respectively. At the end of the experiment, modeling situation was detected by X-ray, pathological changes of cartilage was detected by HE staining ,and apoptosis of chondrocytes was checked by TUNEL staining; mRNA expressions of Caspase-3 and proliferating cell unclear antigen (PCNA) in chondrocytes were detected by RT-PCR; protein expressions of Caspase-3, PCNA, Bcl-2 and Bax in chondrocytes were detected by Western blot. RESULTS: HE stain demonstrated that the chondrocytes of A group,C group and D group were arranged in a more regular and smooth surface when compared with B group. The expressions of Bcl-2 and PCNA in C and D groups were higher than those of B group, but the expression of Caspase-3 and Bax were lower, when evaluated with Western blot;increased expressions of PCNA and Bcl-2 but decreased expressions of Caspase-3 and Bax in C group were also noticed when compared with D group. RT-PCR results demonstrated that when compared with B group, the expression of PCNA mRNA were increased but Caspase-3 mRNA were decreased in C and D groups; compared with D group, the expression of PCNA mRNA were increased but Caspase-3 mRNA were decreased in C group. CONCLUSIONS: The electroacupuncture with near-to-bone needling method is superior to the electroacupuncture with ordinary needling in decreasing apoptosis and promoting proliferation of chondrocytes.

Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains.

Antidepressant activity of N-methyl-D-aspartate (NMDA) receptor antagonists and negative allosteric modulators (NAMs) has led to increased investigation of their behavioral pharmacology. NMDA antagonists, such as ketamine, impair cognition in multiple species and in multiple cognitive domains. However, studies with NR2B subtype-selective NAMs have reported mixed results in rodents including increased impulsivity, no effect on cognition, impairment or even improvement of some cognitive tasks. To date, the effects of NR2B-selective NAMs on cognitive tests have not been reported in nonhuman primates. The current study evaluated two selective NR2B NAMs, CP101,606 and BMT-108908, along with the nonselective NMDA antagonists, ketamine and AZD6765, in the nonhuman primate Cambridge Neuropsychological Test Automated Battery (CANTAB) list-based delayed match to sample (list-DMS) task. Ketamine and the two NMDA NR2B NAMs produced selective impairments in memory in the list-DMS task. AZD6765 impaired performance in a non-specific manner. In a separate cohort, CP101,606 impaired performance of the nonhuman primate CANTAB visuo-spatial Paired Associates Learning (vsPAL) task with a selective impairment at more difficult conditions. The results of these studies clearly show that systemic administration of a selective NR2B NAM can cause transient cognitive impairment in multiple cognitive domains.

Effect of acute NR2B antagonist treatment on long-term potentiation in the rat hippocampus.

The long lasting antidepressant response seen following acute, i.v. ketamine administration in patients with treatment-resistant depression (TRD) is thought to result from enhanced synaptic plasticity in cortical and hippocampal circuits. Using extracellular field recordings in rat hippocampal slices, we show that a single dose of the non-selective NMDA receptor antagonist ketamine or CP-101,606, a selective antagonist of the NR2B subunit of the NMDA receptor, enhances hippocampal synaptic plasticity induced with high frequency stimulation (HFS) 24h after dosing - a time at which plasma concentrations of the drug are no longer detectable in the animal. These results indicate that acute inhibition of NMDA receptors containing the NR2B subunit can lead to long-lasting changes in hippocampal plasticity.

Bioanalysis of (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268) in rat plasma using derivatization liquid chromatography/mass spectrometry.

BACKGROUND: (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid, also known as LY379268, a group II metabotropic glutamate receptor agonist, has been widely used in neuroscience as a model compound in studies evaluating antipsychotic drugs for the treatment of schizophrenia. MATERIALS & METHODS: So far, no reports describing methods of the bioanalysis of LY379268 have been published. Here, a novel method is presented for determining LY379268 in rat plasma employing precolumn derivatization with pentafluorobenzoyl chloride reagent coupled to liquid chromatography/mass spectrometry. CONCLUSION: Chemical derivatization of a low-molecular-weight and highly polar molecule yields a derivative that is retained on a reversed-phase liquid chromatography column with improved tandem mass spectrometric response.