Piezo1 regulates migration and invasion of breast cancer cells via modulating cell mechanobiological properties.

Cell migration and invasion are two essential processes during cancer metastasis. Increasing evidence has shown that the Piezo1 channel is involved in mediating cell migration and invasion in some types of cancers. However, the role of Piezo1 in the breast cancer and its underlying mechanisms have not been clarified yet. Here, we show that Piezo1 is high-expressed in breast cancer cell (BCC) lines, despite its complex expression in clinical patient database. Piezo1 knockdown (Piezo1-KD) promotes unconfined BCC migration, but impedes confined cell migration. Piezo1 may mediate BCC migration through the balances of cell adhesion, cell stiffness, and contractility. Furthermore, Piezo1-KD inhibits BCC invasion by impairing the invadopodium formation and suppressing the expression of metalloproteinases (MMPs) as well. However, the proliferation and cell cycle of BCCs are not significantly affected by Piezo1. Our study highlights a crucial role of Piezo1 in regulating migration and invasion of BCCs, indicating Piezo1 channel might be a new prognostic and therapeutic target in BCCs.

Carbon monoxide augments electrical signaling in cultured neural networks of hippocampal neurons partly through activation of BKCa channels.

Carbon monoxide (CO) is often viewed as a lethal gas in light of its capacity to prevent oxygen uptake in hemoglobin; however, it also functions to regulate a variety of proteins and physiological processes. Here we show that CO is an important chemical cue, to which neurons respond strongly, and this response is then integrated into neural network activity. In cultured mouse hippocampal neurons, CO enhanced synchronized spontaneous cytosolic Ca(2+) oscillations which arose from periodic action potentials through synaptic transmission. We used single-cell patch-clamp recording to investigate the neural network. Our results showed that the frequency of spontaneous and miniature post synaptic current was increased in neurons cultured for 14-18 days after addition of CO, with no change in current amplitude. BK channels have recently been demonstrated to be important in the action of CO. Our results showed that the effect of CO on neural network electrical activity was partly abolished after blocking the BK channels. Altogether, our results suggest that CO can influence neural network electrical activity and that BK channels participate in this regulation process.

The Effectiveness of a Self-Efficacy-Focused Structured Education Program (SSEP) in Improving Metabolic Control and Psychological Outcomes of Type 2 Diabetes Patients: A 12-Month Follow-Up of a Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The 12-month follow-up effect of the self-efficacy-focused structured education program (SSEP) requires in-depth confirmation. This study aims to verify whether the benefits of SSEP can be maintained in 12 months. MATERIALS AND METHODS: A multicenter randomized controlled trial with 12-month follow-up conducted among 265 type 2 diabetes patients not on insulin from 4 hospitals in mainland China. The intervention group (n = 133) was administrated with SSEP, and the control group (n = 132) received the routine education. The indicators of metabolic and psychosocial aspects of the patients were assessed at baseline and 12 months. RESULTS: As opposed to the control group, the primary outcomes of HbA1c in the intervention group were improved obviously in the 12th month during the 12-month follow-up (-1.13%, P < 0.001). The secondary outcomes (ie, waist circumference, total cholesterol, low-density lipoprotein cholesterol, diabetes self-efficacy, diabetes self-management behaviors, diabetes knowledge and diabetes distress) were improved significantly in the intervention group as compared with the control group in the 12th month during the 12-month follow-up (-3.14 cm, P = 0.001; -0.30 mmol/L, P = 0.032; -0.25 mmol/L, P = 0.008; 0.87, P < 0.001; 10.67, P < 0.001; 3.42, P < 0.001; -4.97, P < 0.001). The non-significant difference in the secondary outcomes (ie, systolic pressure, diastolic pressure, triglycerides and high-density lipoprotein cholesterol) was identified between the two groups in the 12th month during the 12-month follow-up (P > 0.05). CONCLUSION: The SSEP provided sustainable benefits in outcomes of HbA1c, waist circumference, total cholesterol, low-density lipoprotein cholesterol, diabetes knowledge, diabetes distress, diabetes self-efficacy and diabetes self-management behaviors for type 2 diabetes patients not on insulin in the 12th month during the 12-month follow-up. Thus, it will be an effective education model capable of being generalized nationwide, and it can be referenced for the nations and regions under consistent conditions. CLINICAL TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR-IOR-17011007).

Microniche geometry modulates the mechanical properties and calcium signaling of chondrocytes.

In articular cartilage, the function of chondrocytes is strongly related to their zone-specific microniche geometry defined by pericellular matrix. Microniche geometry is critical for regulating the phenotype and function of the chondrocyte in native cartilage and tissue engineering constructs. However the role of microniche geometry in the mechanical properties and calcium signaling of chondrocytes remains unknown. To recapitulate microniche geometry at single-cell level, we engineered three basic physiological-related polydimethylsiloxane (PDMS) microniches geometries fabricated using soft lithography. We cultured chondrocytes in these microniche geometries and quantified cell mechanical properties using atomic force microscopy (AFM). Fluorescent calcium indicator was used to record and quantify cytosolic Ca2+ oscillation of chondrocytes in different geometries. Our work showed that microniche geometry modulated the mechanical behavior and calcium signaling of chondrocytes. The ellipsoidal microniches significantly enhanced the mechanical properties of chondrocytes compared to spheroidal microniche. Additionally, ellipsoidal microniches can markedly improved the amplitude but weakened the frequency of cytosolic Ca2+ oscillation in chondrocytes than spheroidal microniche. Our work might reveal a novel understanding of chondrocyte mechanotransduction and therefore be useful for designing cell-instructive scaffolds for functional cartilage tissue engineering.

[The development of a dispensing cabinet of total nutrient admixture].

A dispensing cabinet of total nutrient admixture is introduced in this paper. Which can be used for nutrient solution dispensing. The clinical application shows that it can provide a practical, simple, safe and satisfactory sterile environment.

Stiff substrates enhance cultured neuronal network activity.

The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.

[A randomized controlled trail of taxol-based combination regimens for advanced gastric cancer].

BACKGROUND & OBJECTIVE: Standard chemotherapy for advanced gastric cancer remains undefined. Phase II trials show that taxol is effective in treating advanced gastric cancer. This multi-center prospective open randomized controlled study was to compare the efficacy of Taxol plus calcium folinate (CF)/5-fluorouracil (5-FU), Taxol plus oxaliplatin (OXA), and CF/5-FU plus cisplatin (DDP) on advanced gastric cancer, and analyze their toxicities. METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma were randomized into CF/5-FU+DDP (control), CF/5-FU + Taxol, and Taxol + OXA groups, and received up to 8 cycles of chemotherapy. Treatment efficacy and adverse events were evaluated according to WHO criteria. RESULTS: A total of 180 patients were enrolled from May 2002 to May 2004, and randomized into the 3 groups; each group contained 60 patients. Of the 180 patients, 14 received 2 cycles of chemotherapy, 49 received 4 cycles, and 103 received 8 cycles. Treatment outcomes of 166 cases were evaluable. The response rate (RR) of naive patients or the patients with retroperitoneal lymph node metastasis was significantly higher in CF/5-FU+Taxol and Taxol+OXA groups than in control group (50.00% and 80.00% vs. 20.75%, P<0.05; 65.96% and 85.71% vs. 36.36%, P<0.05). But the RR of the patients with liver metastasis was similar among the 3 groups (28.57% and 39.13% vs. 34.62%, P>0.05). The occurrence rates of nausea/vomiting, anepithymia, stomatitis, and kidney damage were lower in study groups than in control group, but the occurrence rates of myelosuppression and peripheral nerve damage were higher in study groups than in control group. Allergic response occurred in 7 (5.88%) patients in study group, and 3 (2.52%) of them were serious. There was no treatment-related death. CONCLUSIONS: Despite its hematotoxicity, the treatment efficacy of Taxol-based combination regimens on advanced gastric cancer is better than that of CF/5-FU + DDP regimen with tolerable toxicities. We recommend Taxol-based combination regimens as first-line regimens for advanced gastric cancer.