Evaluation of a Positron Emission Tomography Tracer Targeting Colony-Stimulating Factor 1 Receptor for Detecting Pulmonary Inflammation.

Colony-stimulating factor 1 receptor (CSF1R) is a type III receptor tyrosine kinase that is crucial for immune cell activation, survival, proliferation, and differentiation. Its expression significantly increases in macrophages during inflammation, playing a crucial role in regulating inflammation resolution and termination. Consequently, CSF1R has emerged as a critical target for both therapeutic intervention and imaging of inflammatory diseases. Herein, we have developed a radiotracer, 1-[4-((7-(dimethylamino)quinazolin-4-yl)oxy)phenyl]-3-(4-[18F]fluorophenyl)urea ([18F]17), for in vivo positron emission tomography (PET) imaging of CSF1R. Compound 17 exhibits a comparable inhibitory potency against CSF1R as the well-known CSF1R inhibitor PLX647. The radiosynthesis of [18F]17 was successfully performed by radiofluorination of aryltrimethyltin precursor with a yield of approximately 12% at the end of synthesis, maintaining a purity exceeding 98%. In vivo stability and biodistribution studies demonstrate that [18F]17 remains >90% intact at 30 min postinjection, with no defluorination observed even at 60 min postinjection. The PET/CT imaging study in lipopolysaccharide-induced pulmonary inflammation mice indicates that [18F]17 offers a more sensitive characterization of pulmonary inflammation compared to traditional [18F]FDG. Notably, [18F]17 shows a higher discrepancy in uptake ratio between mice with pulmonary inflammation and the sham group. Furthermore, the variations in [18F]17 uptake ratio observed on day 7 and day 14 correspond to lung density changes observed in CT imaging. Moreover, the expression levels of CSF1R on day 7 and day 14 follow a trend similar to the uptake pattern of [18F]17, indicating its potential for accurately characterizing CSF1R expression levels and effectively monitoring the pulmonary inflammation progression. These results strongly suggest that [18F]17 has promising prospects as a CSF1R PET tracer, providing diagnostic opportunities for pulmonary inflammatory diseases.

Effects of ovarian endometrioma aspiration on in vitro fertilization-intracytoplasmic sperm injection and embryo transfer outcomes: a systematic review and meta-analysis.

PURPOSE: To evaluate the effect of ovarian endometrioma aspiration on IVF/ICSI outcomes. METHODS: The PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched to identify studies related to the treatment of endometrioma up to October 1, 2020, and the data of 1207 patients from 10 studies were analyzed using STATA. RESULTS: The 10 studies in our analysis included 7 comparing aspiration and surgery and 6 comparing aspiration with no intervention. In the aspiration versus surgery groups, live birth rate [OR 0.97 (95% CI 0.51, 1.85), P = 0.925] and clinical pregnancy rate [OR 1.30 (95% CI 0.95, 1.80), P = 0.105] showed no significant difference between the two groups. Abortion rate [OR 4.26 (95% CI 1.38, 13.08), P = 0.011], the number of oocytes retrieved [mean difference 1.95 (95% CI 0.10, 3.81), P = 0.039], and the estradiol peak on hCG day [mean difference 392.16 (95% CI 230.14, 554.18), P < 0.001] were significantly higher in the aspiration group compared to the surgical group. In the aspiration versus the no intervention group, live birth rate [OR 0.84 (95% CI 0.45, 1.59), P = 0.602] and clinical pregnancy rate [OR 1.25 (95% CI 0.88, 1.77), P = 0.206] were not significantly different between the two groups. The abortion rate [OR 0.31 (95% CI 0.11, 0.88), P = 0.028] and the number of gonadotropin ampoules [mean difference - 3.13 ampoules (95% CI - 4.90, - 1.37), P < 0.001] were significantly lower in the aspiration group compared to the no intervention group. CONCLUSION: Compared with surgical treatment or no intervention treatment, aspiration has less effect on ovarian response, ovarian reserve, and pregnancy outcomes.

[Textual research on varieties of Draconis Sanguis].

This paper reviewed the historical evolution of the varieties of Draconis Sanguis in traditional Chinese medicine(TCM) and discussed several doubts. Draconis Sanguis used in ancient Europe and Arabia was derived from Dracaena plants, and that originating from Southeast Asia entered the market in the 16 th century. Draconis Sanguis was introduced into China in the 5 th century at the latest and was once mixed with shellac for use. Draconis Sanguis in the Tang Dynasty and before was the resin of Dracaena plants. Scholars in the Song Dynasty have known that Draconis Sanguis came from the resin of tall trees, but their understanding of origin plants was inconsistent with the facts. The origin of Draconis Sanguis in the Song Dynasty was basically determined to be Mirbat(Maliba), Cengtan, and Somali, as well as Socotra Archipelago. About 1371-1416, Draconis Sanguis prepared from Daemonorops draco was imported into China, and was recorded earlier in The Overall Survey of the Ocean's Shores(Ying Ya Sheng Lan) and Code of Great Ming Dynasty(Da Ming Hui Dian). Draconis Sanguis prepared from Dracaena plants was still authentic for a long time after the import of that from D. draco into China. During the Ming and Qing Dynasties, Dian Zhi(1625), a lost edition of Materia Medica in Southern Yunnan(Dian Nan Ben Cao), Textual Research on Reality and Titles of Plants(Zhi Wu Ming Shi Tu Kao), and other local chronicles recorded that a new type of Draconis Sanguis(Mu Xue Jie) was produced in Yuanjiang, Yunnan province. The New Yunnan Chronicles of the Republic of China recorded the production of another type of Draconis Sanguis(Qi Lin Jie) in Xishuangbanna. However, the authenticity of the above two types has been difficult to confirm. In modern times, Draconis Sanguis prepared from D. draco gradually became the mainstream variety. In the 1970 s, Dracaena cochinchinensi was found in Yunnan and other provinces, and Draconis Sanguis from D. cochinchinensi was developed. This study is expected to provide a solid and reliable literature support for the research and development of Draconis Sanguis, enrich historical materials, and provide new clues for follow-up research.

Hydrogen-Bond-Donor Solvents Enable Catalyst-Free (Radio)-Halogenation and Deuteration of Organoborons.

A hydrogen bond donor solvent assisted (radio)halogenation and deuteration of organoborons has been developed. The reactions exhibited high functional group tolerance and needed only an ambient atmosphere. Most importantly, compared to literature methods, our conditions are more consistent with the principals of green chemistry (e.g., metal-free, strong oxidant-free, more straightforward conditions).

Modulation of Spinal Nociceptive Transmission by Sub-Sensory Threshold Spinal Cord Stimulation in Rats After Nerve Injury.

OBJECTIVES: High-frequency spinal cord stimulation (SCS) administered below the sensory threshold (subparesthetic) can inhibit pain, but the mechanisms remain obscure. We examined how different SCS paradigms applied at intensities below the threshold of Aß-fiber activation (sub-sensory threshold) affect spinal nociceptive transmission in rats after an L5 spinal nerve ligation (SNL). MATERIALS AND METHODS: Electrophysiology was used to record local field potential (LFP) at L4 spinal cord before, during, and 0-60 min after SCS in SNL rats. LFP was evoked by high-intensity paired-pulse test stimulation (5 mA, 0.2 msec, 400 msec interval) at the sciatic nerve. Epidural SCS was delivered through a miniature electrode placed at T13-L1 and L2-L3 spinal levels. Four patterns of SCS (200 Hz, 1 msec; 500 Hz, 0.5 msec; 1200 Hz; 0.2 msec; 10,000 Hz, 0.024 msec, 30 min, bipolar) were tested at 90% Aß-threshold as a subthreshold intensity. As a positive control, traditional SCS (50 Hz, 0.2 msec) was tested at 100% Aß-plateau as a suprathreshold intensity. RESULTS: Traditional suprathreshold SCS at T13-L1 level significantly reduced LFP to C-fiber inputs (C-LFP). Subthreshold SCS of 200 and 500 Hz, but not 1200 or 10,000 Hz, also reduced C-LFP, albeit to a lesser extent than did traditional SCS (n = 7-10/group). When SCS was applied at the L2-L3 level, only traditional SCS and subthreshold SCS of 200 Hz inhibited C-LFP (n = 8-10/group). CONCLUSIONS: Traditional suprathreshold SCS acutely inhibits spinal nociceptive transmission. Low-frequency subthreshold SCS with a long pulse width (200 Hz, 1 msec), but not higher-frequency SCS, also attenuates C-LFP.

Paclitaxel, 5-fluorouracil, and leucovorin combination chemotherapy as first-line treatment in patients with advanced gastric cancer.

The aim of this retrospective analysis was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, 5-fluorouracil, and leucovorin (TFL) as first-line treatment in patients with advanced gastric cancer (AGC). One hundred and thirteen patients were enrolled in the study who were confirmed to have AGC by histopathology. These patients were treated with TFL: paclitaxel at a dose of 135 mg/m as a 3-h intravenous infusion on day 1, LV 400 mg/m as an intravenous infusion over 2 h on day 1, followed by 5-fluorouracil 2400 mg/m as an infusion over a 46-h period on 3 consecutive days. Cycles were repeated every 2 weeks. A total of 113 patients were assessed for their response to therapy. A total of three patients achieved complete responses and 46 patients achieved partial responses, yielding an overall objective response rate of 43.4% [95% confidence interval (CI): 34.3-52.5%]. Fifty-four cases of stable disease and 10 cases of progressive disease were observed in the remaining patients. The median time to progression and overall survival were 5.2 months (95% CI: 4.7-5.8 months) and 14.1 months (95% CI: 12.5-15.8 months), respectively. Toxicities were tolerable and moderate. The most common grade 3-4 toxicities included leukopenia (16.8%), neutropenia (17.7%), anemia (8.0%), thrombocytopenia (5.3%), and fatigue (6.2%). Combination chemotherapy with TFL offers an active and safe therapeutic approach for patients with AGC.

Sporamin induces apoptosis and inhibits NF-κB activation in human pancreatic cancer cells.

Sporamin, a Kunitz-type trypsin inhibitor (TI) from sweet potato tuberous roots, has demonstrated anti-tumor activity through poorly defined mechanisms. Furthermore, the effects of sporamin on pancreatic cancer have not been explored. Herein, we studied the effects of sporamin on two human pancreatic cancer cell lines, PANC-1 and BxPC-3. Sporamin significantly inhibited the cell viability and proliferation activity and induced apoptosis in PANC-1 and BxPC-3 cells. Consistently, in sporamin-treated PANC-1 and BxPC-3 cells, the anti-apoptotic proteins Bcl-2 and Bcl-XL were downregulated and the pro-apoptotic protein Bax was upregulated. Moreover, nuclear factor kappa B activation and IκBα phosphorylation were inhibited, and total IκBα expression was increased in sporamin-treated PANC-1 and BxPC-3 cells. Thus, our results suggest that the anti-tumor effects of sporamin in pancreatic cancer cells might result partly from induction of apoptosis by downregulating nuclear factor kappa B pathway.

Cyanobacterial chassis engineering for enhancing production of biofuels and chemicals.

To reduce dependence on fossil fuels and curb greenhouse effect, cyanobacteria have emerged as an important chassis candidate for producing biofuels and chemicals due to their capability to directly utilize sunlight and CO2 as the sole energy and carbon sources, respectively. Recent progresses in developing and applying various synthetic biology tools have led to the successful constructions of novel pathways of several dozen green fuels and chemicals utilizing cyanobacterial chassis. Meanwhile, it is increasingly recognized that in order to enhance productivity of the synthetic cyanobacterial systems, optimizing and engineering more robust and high-efficient cyanobacterial chassis should not be omitted. In recent years, numerous research studies have been conducted to enhance production of green fuels and chemicals through cyanobacterial chassis modifications involving photosynthesis, CO2 uptake and fixation, products exporting, tolerance, and cellular regulation. In this article, we critically reviewed recent progresses and universal strategies in cyanobacterial chassis engineering to make it more robust and effective for bio-chemicals production.

Acupuncture at homotopic acupoints exerts dual effects on bladder motility in anesthetized rats.

BACKGROUND: In Chinese medicine, dual effects on target organs are considered a primary characteristic of acupoint. Acupoints may be classified as heterotopic or homotopic in terms of spinal segmental innervation: homotopic acupoints contain afferent innervation in the same segment from which efferent fibers innervate target visceral organs, and heterotopic acupoints utilize different spinal segments to innervate target visceral organs than the segment receiving the afferent signal. It is well-known that dual effects of acupuncture on the bladder can be generated based on different states of the bladder, however, the dual effects of single acupoint stimulation and acupoint site-specificity (homotopic acupoints and heterotopic acupoints) on the bladder have yet to be investigated. METHODS: Twenty Sprague-Dawley rats were anesthetized and the intravesical pressure was measured via a manometric balloon inserted into the bladder. The acupuncture needle was separately inserted to a depth of 4 mm at the acupoints RN1 (Huiyin), RN3 (Zhongji), BL28 (Pangguangshu), BL32 (Ciliao), RN2 (Qugu) or BL23 (Shenshu), and manually rotated right then left with a frequency of 2 Hz for 1 min. Following acupuncture stimulation, bladder pressure was recorded and compared against the pre-stimulation measurements. RESULTS: During the bladder's active state, manual acupuncture (MA) at RN1, RN3, BL28, BL32 or RN2 inhibited bladder motility (P < 0.01). In the static bladder, MA at RN1, RN3, BL28, BL32, RN2 or BL23 increased bladder motility (P < 0.01). CONCLUSIONS: MA at homotopic acupoints may produce dual effects on bladder motility: inhibiting bladder motility when in an active state and enhancing bladder motility when in a static state.

Effect of scraping therapy on weightlifting ability.

OBJECTIVE: To verify the effects of scraping therapy on the weightlifting ability by measuring the subjective sensation, and changes of biomarkers. METHODS: Five students, who have been trained for 3 years in a sport school in China were participated in this study. A course of scraping therapy was applied to intervene during the normal 7-week of weightlifting training programme. The ability of weightlifting, the scale of rating perceived exertion and serum biochemical markers were measured before and after the intervention. RESULTS: Scraping therapy caused a significant increase in weightlifting ability (P < 0.05). The level of rating perceived exertion remained stable with the increase in the training volume. Immuno-globulin A was significantly increased (P < 0.05), and creatine kinase and blood urea nitrogen were significantly decreased (P < 0.05). No significant changes were observed in white blood cell, neutrophil, and testosterone. CONCLUSION: Scraping therapy may facilitate weightlifting ability mainly by decreasing weight sensation and improving serum biochemical parameters.

Promoting high-quality development of acupuncture and moxibustion. / 推进针灸学科的高质量发展.

In the past 20 years, the acupuncture-moxibustion discipline has made a great progress in clinical research, method construction, standard formulation, guideline promotion, basic theory and key scientific issue research. Internationally, the development of acupuncture and moxibustion has gradually begun to pay more attention to the basic issues of the discipline itself from focusing on clinical evidence. The National Institute of Health of USA pays close attention to the construction of acupoint knowledge base and database and to the transformation of peripheral nerve stimulation techniques, which brings forth opportunities and challenges for the development of acupuncture-moxibustion discipline. In the present paper, we analyze the shortcomings of the current development of acupuncture and moxibustion, put forward some strategies for high-quality development in the future, and sort out the basic scientific issues to form an academic consensus. We should employ modern scientific language to express the scientific connotations of the basic theory of acupuncture and moxibustion, and build an open and self-consistent modern theoretical system. In addition, we also should attract more multidisciplinary talents to harmoniously and assiduously work together, insist on continuous innovation to open up a new situation in the transformation of basic scientific research achievements, and establish a new theoretical system of "somato-medicine" represented by acupuncture and moxibustion. In this way, we will guide the acupuncture-moxibustion discipline to make an original contribution to the modern life science and future medicine.

Continuous peripheral electrical nerve stimulation improves cardiac function via autonomic nerve regulation in MI rats.

BACKGROUND: Peripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac function based on cardiac self-repair is not well understood. OBJECTIVES: This study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. METHODS: The activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to evaluate the autonomic tone directly. The pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. RESULTS: Sympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS at acupoint PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS at acupoint ST36 had a limited effect. Both iPENS at PC6 and ST36 improved the autonomic and cardiac function of rats in the cPENS groups. CONCLUSION: Rats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

In Vivo Calcium Imaging of Dorsal Root Ganglia Neurons' Response to Somatic and Visceral Stimuli.

A technique is described for surgically exposing the dorsal root ganglion (DRG) of the lumbar-6 in a live, anesthetized laboratory mouse, along with the protocol for in vivo calcium imaging of the exposed DRG in response to various visceral and somatic stimuli. Pirt-GCaMP6s mice or C57BL6 mice intrathecally injected with AAV viruses packaged with GCaMP6s were utilized to capture Ca2+ transients. The amplitude of these transients indicates sensitivity to specific sensory modalities. Afferent fibers originate from internal organs, with primary neuronal cell bodies in spinal or vagal ganglia. Studies on visceral nociception and acupuncture analgesia can potentially be conducted on primary sensory neurons using advanced imaging technologies like in vivo calcium imaging, allowing for the recording of neuronal activity ensembles in the intact animal during stimulation or intervention. The responses of DRG neuron ensembles to somatic and visceral stimuli applied to their corresponding receptive fields were recorded. This technique illustrates how neuronal populations react to various types of somatic and visceral stimuli. It is possible to comprehensively compare neuronal ensemble responses to different stimuli, which is a particularly valuable approach in research on visceral pain and segmental mechanisms of somatic stimulation, such as acupuncture.

Erratum: In Vivo Calcium Imaging of Dorsal Root Ganglia Neurons' Response to Somatic and Visceral Stimuli.

This corrects the article 10.3791/65975.

Perspective of Calcium Imaging Technology Applied to Acupuncture Research.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

Caffeine Impaired Acupuncture Analgesia in Inflammatory Pain by Blocking Adenosine A1 Receptor.

Caffeine consumption inhibits acupuncture analgesic effects by blocking adenosine signaling. However, existing evidence remains controversial. Hence, this study aimed to examine the adenosine A1 receptor (A1R) role in moderate-dose caffeine-induced abolishing effect on acupuncture analgesia using A1R knockout mice (A1R-/-). We assessed the role of A1R in physiological sensory perception and its interaction with caffeine by measuring mechanical and thermal pain thresholds and administering A1R and adenosine 2A receptor antagonists in wild-type (WT) and A1R-/- mice. Formalin- and complete Freund's adjuvant (CFA)-induced inflammatory pain models were recruited to explore moderate-dose caffeine effect on pain perception and acupuncture analgesia in WT and A1R-/- mice. Moreover, a C-fiber reflex electromyogram in the biceps femoris was conducted to validate the role of A1R in the caffeine-induced blockade of acupuncture analgesia. We found that A1R was dispensable for physiological sensory perception and formalin- and CFA-induced hypersensitivity. However, genetic deletion of A1R impaired the antinociceptive effect of acupuncture in A1R-/- mice under physiological or inflammatory pain conditions. Acute moderate-dose caffeine administration induced mechanical and thermal hyperalgesia under physiological conditions but not in formalin- and CFA-induced inflammatory pain. Moreover, caffeine significantly inhibited electroacupuncture (EA) analgesia in physiological and inflammatory pain in WT mice, comparable to that of A1R antagonists. Conversely, A1R deletion impaired the EA analgesic effect and decreased the caffeine-induced inhibitory effect on EA analgesia in physiological conditions and inflammatory pain. Moderate-dose caffeine administration diminished the EA-induced antinociceptive effect by blocking A1R. Overall, our study suggested that caffeine consumption should be avoided during acupuncture treatment. PERSPECTIVE: Moderate-dose caffeine injection attenuated EA-induced antinociceptive effect in formalin- and CFA-induced inflammatory pain mice models by blocking A1R. This highlights the importance of monitoring caffeine intake during acupuncture treatment.

Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.

Sympathetic-Sensory Coupling as a Potential Mechanism for Acupoints Sensitization.

A series of studies have demonstrated acupoint sensitization, in which acupoints can be activated in combination with sensory hypersensitivity and functional plasticity during visceral disorders. However, the mechanisms of acupoint sensitization remain unclear. Neuroanatomy evidence showed nociceptors innervated in acupoints contribute to the mechanism of acupoint sensitization. Increasing studies suggested sympathetic nerve plays a key role in modulating sensory transmission by sprouting or coupling with sensory neuron/nociceptor in the peripheral, forming the functional structure of the sympathetic-sensory coupling. Notably, the sensory inputs of the disease-induced sensitized acupoint contribute to the homeostatic regulation and also involve in delivering therapeutic information under acupuncture, hence, the role of sprouted sympathetic in acupoint function should be given attention. We herein reviewed the current knowledge of sympathetic and its sprouting in pain modulation, then discussed and highlighted the potential value of sympathetic-sensory coupling in acupoint functional plasticity.

Silencing Rac1 and Prex1 Inhibit Epithelial-Mesenchymal Transition in Human Gastric Cancer Cells Induced by Transforming Growth Factor-ß1.

BACKGROUND/AIMS: Transforming growth factor-beta can influence tumor cells, causing epithelial-mesenchymal transition and enhancing their invasion and metastasis ability. Rac1 protein could be used as an independent tumor diagnostic marker and survival predictor. Prex1 is closely related to cell metastasis. In this study, the impact of silencing Rac1 and Prex1 on transforming growth factor-beta 1-induced epithelial-mesenchymal transition and apoptosis of human gastric cancer cells MGC-803 and MKN45 was investigated. MATERIALS AND METHODS: MGC-803 and MKN45 cells received recombinant transforming growth factor-beta 1 (rTGF-ß1) treatments at various concentrations. Cell Counting Kit-8 kit was used to determine cell viability. Rac1 and Prex1 interference vectors were transfected into the rTGF-ß1-treated MGC-803 and MKN45 cells. Cell apoptosis and migration were detected by flow cytometry and scratch test, respectively. Western blot was used to detect the epithelial-mesenchymal transition-related markers E-cadherin, N-cadherin, vimentin, and PDLIM2 expression levels. RESULTS: The rTGF-ß1 (10 ng/mL) could promote MGC-803 and MKN45 cell viability. Silencing Rac1 and Prex1 could increase E-cadherin and PDLIM2 expression, decrease N-cadherin and vimentin expression, inhibit cell viability and migration, and promote apoptosis in rTGF-ß1-treated MGC-803 and MKN45 cells. CONCLUSIONS: Silencing Rac1 and Prex1 could inhibit epithelial-mesenchymal transition, reduce cell viability and migration, and promote apoptosis in human gastric cancer cells.

The Utility of Peripherally Restricted Kappa-Opioid Receptor Agonists for Inhibiting Below-Level Pain After Spinal Cord Injury in Mice.

Pain after spinal cord injury (SCI) can be difficult to treat. Drugs that target the opioid receptor (OR) outside the central nervous system (CNS) have gained increasing interest in pain control owing to their low risk of central side effects. Asimadoline and ICI-204448 are believed to be peripherally restricted KOR agonists withlimited access to the CNS. This study examined whether they can attenuate pain hypersensitivity in mice subjected to a contusive T10 SCI. Subcutaneous (s.c.) injection of asimadoline (5, 20 mg/kg) and ICI-204448 (1, 10 mg/kg) inhibited heat hypersensitivity at both doses, but only attenuated mechanical hypersensitivity at the high dose. However, the high-dose asimadoline adversely affected animals' exploratory performance in SCI mice and caused aversion, suggesting CNS drug penetration. In contrast, high-dose ICI-204448 did not impair exploration and remained effective in reducing both mechanical and heat hypersensitivities after SCI. Accordingly, we chose to examine the potential peripheral neuronal mechanism for ICI-204448-induced pain inhibition by conducting in vivo calcium imaging of dorsal root ganglion (DRG) in Pirt-GCaMP6s+/- mice. High-dose ICI-204448 (10 mg/kg, s.c.) attenuated the increased fluorescence intensity of lumbar DRG neurons activated by a noxious pinch (400 g) stimulation in SCI mice. In conclusion, systemic administration of ICI-204448 achieved SCI pain inhibition at doses that did not induce notable side effects and attenuated DRG neuronal excitability which may partly contribute to its pain inhibition. These findings suggest that peripherally restricted KOR agonists may be useful for treating SCI pain, but the therapeutic window must be carefully examined.