Stimulated Cell Proliferation Research Articles

Particulate reinforced bone cements: The potential antibacteric role of nitrides

In recent years, silicon nitride (Si3N4) ceramics have gained popularity as bioactive structural materials with the capability to stimulate cell proliferation and fight pathogens. Despite displaying bioactive properties and having an excellent mechanical strength, the number of possible applications for silicon nitride is somehow limited by its brittle nature and high production costs. In this work, particles of Si3N4 have been added to Poly(methyl metachylate) (PMMA) bone cements to verify how this reinforcement influences mechanical and antibacterial properties. 5, 10 and 15% weight fractions of powders with average mesh size 25, 50 and 300 μm were mixed together with PMMA and molded into testing samples. Results of the in vitro testing with Escherichia coli and Staphylococcus epidermidis showed that the antibacterial effects of Si3N4 correlate positively with the fraction of ceramic used and are negatively correlated with the mesh size of the powders. Moreover, the smaller particles at the lowest concentration acted as a mechanical reinforcement, increasing the ultimate tensile strength of the composite by about 10%.

CircPLXNA2 Affects the Proliferation and Apoptosis of Myoblast through circPLXNA2/gga-miR-12207-5P/MDM4 Axis

CircRNAs are newly identified special endogenous RNA molecules that covalently close a loop by back-splicing with pre-mRNA. In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, knowledge of circRNA functional alternation in skeletal myogenesis is still in its infancy. In this study, we identified a circRNA-miRNA-mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts' (CPMs) myogenesis by multi-omics (i.e., circRNA-seq and ribo-seq). In total, 314 circRNA-miRNA-mRNA regulatory axes containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, the circPLXNA2-gga-miR-12207-5P-MDM4 axis aroused our research interest. The circPLXNA2 is highly differentially expressed during differentiation versus proliferation. It was demonstrated that circPLXNA2 inhibited the process of apoptosis while at the same time stimulating cell proliferation. Furthermore, we demonstrated that circPLXNA2 could inhibit the repression of gga-miR-12207-5p to MDM4 by directing binding to gga-miR-12207-5p, thereby restoring MDM4 expression. In conclusion, circPLXNA2 could function as a competing endogenous RNA (ceRNA) to recover the function of MDM4 by directing binding to gga-miR-12207-5p, thereby regulating the myogenesis.

Eukaryotic Translation Initiation Factor 3 Subunit D is One Clinical Target and Pre-Tumor Gene for Non Hodgkin Lymphoma to Promote Cell Proliferation Through Warburg Effect by Interacting with GRP78

Non-Hodgkin’s lymphoma (NHL) is one highly heterogeneous tumor originating from the lymphatic system. Its morbidity rate shows a gradually increasing trend year by year. The present study determined that the possible function and mechanisms of EIF3D on cell proliferation of NHL. A total of 24 patients with NHL were obtained at Aerospace Center Hospital. In patients with NHL, mRNA and protein expression of EIF3D was up-regulated. Patients with low EIF3D possessed better survival rate. EIF3D stimulated cell proliferation and the number of Edu cells through the activation of Warburg effect in vitro model of NHLNHL. Sh-EIF3D diminished NHL cell proliferation and the number of Edu cells through the inactivation of Warburg effect in vitro model of NHL. Then, we found that EIF3D reduced GRP78 protein ubiquitination to induce GRP78/Akt proteins, and si-EIF3D promote GRP78 protein ubiquitination to suppress GRP78/Akt proteins in vitro model of NHL. Our results indicate that EIF3D promote NHL cell proliferation throughWarburg effect by the inhibition of GRP78 protein ubiquitination, suggesting that it may prove to be one clinical target and pre-tumor gene for NHL.

Neuronal nitric oxide synthase is required for erythropoietin stimulated erythropoiesis in mice.

Introduction: Erythropoietin (EPO), produced in the kidney in a hypoxia responsive manner, is required for red blood cell production. In non-erythroid tissue, EPO increases endothelial cell production of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) that regulates vascular tone to improve oxygen delivery. This contributes to EPO cardioprotective activity in mouse models. Nitric oxide treatment in mice shifts hematopoiesis toward the erythroid lineage, increases red blood cell production and total hemoglobin. In erythroid cells, nitric oxide can also be generated by hydroxyurea metabolism that may contribute to hydroxyurea induction of fetal hemoglobin. We find that during erythroid differentiation, EPO induces neuronal nitric oxide synthase (nNOS) and that neuronal nitric oxide synthase is required for normal erythropoietic response. Methods: Wild type (WT) mice and mice with targeted deletion of nNOS (nNOS-/-) and eNOS (eNOS-/-) were assessed for EPO stimulated erythropoietic response. Bone marrow erythropoietic activity was assessed in culture by EPO dependent erythroid colony assay and in vivo by bone marrow transplantation into recipient WT mice. Contribution of nNOS to EPO stimulated cell proliferation was assessed in EPO dependent erythroid cells and in primary human erythroid progenitor cell cultures. Results: EPO treatment increased hematocrit similarly in WT and eNOS-/- mice and showed a lower increase in hematocrit nNOS-/- mice. Erythroid colony assays from bone marrow cells were comparable in number from wild type, eNOS-/- and nNOS-/- mice at low EPO concentration. Colony number increased at high EPO concentration is seen only in cultures from bone marrow cells of wild type and eNOS-/- mice but not from nNOS-/- mice. Colony size with high EPO treatment also exhibited a marked increase in erythroid cultures from wild type and eNOS-/- mice but not from nNOS-/- mice. Bone marrow transplant from nNOS-/- mice into immunodeficient mice showed engraftment at comparable levels to WT bone marrow transplant. With EPO treatment, the increase in hematocrit was blunted in recipient mice that received with nNOS-/- donor marrow compared with recipient mice that received WT donor marrow. In erythroid cell cultures, addition of nNOS inhibitor resulted in decreased EPO dependent proliferation mediated in part by decreased EPO receptor expression, and decreased proliferation of hemin induced differentiating erythroid cells. Discussion: EPO treatment in mice and in corresponding cultures of bone marrow erythropoiesis suggest an intrinsic defect in erythropoietic response of nNOS-/- mice to high EPO stimulation. Transplantation of bone marrow from donor WT or nNOS-/- mice into recipient WT mice showed that EPO treatment post-transplant recapitulated the response of donor mice. Culture studies suggest nNOS regulation of EPO dependent erythroid cell proliferation, expression of EPO receptor and cell cycle associated genes, and AKT activation. These data provide evidence that nitric oxide modulates EPO dose dependent erythropoietic response.

Two-Layered Biomimetic Flexible Self-Powered Electrical Stimulator for Promoting Wound Healing.

The repair of wound damage has been a common problem in clinic for a long time. Inspired by the electroactive nature of tissues and the electrical stimulation of wounds in clinical practice, the next generation of wound therapy with self-powered electrical stimulator is expected to achieve the desired therapeutic effect. In this work, a two-layered self-powered electrical-stimulator-based wound dressing (SEWD) was designed through the on-demand integration of the bionic tree-like piezoelectric nanofiber and the adhesive hydrogel with biomimetic electrical activity. SEWD has good mechanical properties, adhesion properties, self-powered properties, high sensitivity, and biocompatibility. The interface between the two layers was well integrated and relatively independent. Herein, the piezoelectric nanofibers were prepared by P(VDF-TrFE) electrospinning, and the morphology of the nanofibers was controlled by adjusting the electrical conductivity of the electrospinning solution. Benefiting from its bionic dendritic structure, the prepared piezoelectric nanofibers had better mechanical properties and piezoelectric sensitivity than native P(VDF-TrFE) nanofibers, which can convert tiny forces into electrical signals as a power source for tissue repair. At the same time, the designed conductive adhesive hydrogel was inspired by the adhesive properties of natural mussels and the redox electron pairs formed by catechol and metal ions. It has bionic electrical activity matching with the tissue and can conduct the electrical signal generated by the piezoelectric effect to the wound site so as to facilitate the electrical stimulation treatment of tissue repair. In addition, in vitro and in vivo experiments demonstrated that SEWD converts mechanical energy into electricity to stimulate cell proliferation and wound healing. The proposed healing strategy for the effective treatment of skin injury was provided by developing self-powered wound dressing, which is of great significance to the rapid, safe, and effective promotion of wound healing.

Influence of excessive body weight on cancer development and prognosis

Introduction and purpose
 According to the WHO, overweight and obesity are defined as excessive or abnormal accumulation of adipose tissue, leading to deterioration of health. Excessive body weight is a constantly growing public health problem that has reached the scale of a pandemic. Currently, there is ample evidence that excess body weight increases the risk of developing cancer and worsens the prognosis. The aim of this review is to analyze the impact of overweight and obesity on cancer development and prognosis, and to elucidate pathogenesis.
 State of knowledge 
 Based on the current state of knowledge in epidemiology, it is estimated that approximately 20% of all malignancies are related to excessive body weight. So far, there is sufficient evidence to support an association between excess body fat and 13 out of 24 cancer sites: esophagus, gastric cardia, colon, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, meningioma, thyroid and multiple myeloma. Adipose tissue cells produce growth factors, hormones and cytokines that can interfere with the regulation of cell growth and survival. Excess adipose tissue leads to systemic chronic inflammation, oxidative stress, insulin resistance, hyperinsulinemia, increase in sex hormones, increase in leptin levels and a decrease in adiponectin levels. This leads to DNA defects, stimulation of angiogenesis, cell proliferation and inhibition of apoptosis, and thus promotes the development of cancer. In addition, studies have estimated that excess body weight is responsible for 14% of cancer deaths in men and 20% in women.
 Conclusions
 Due to the increasing problem of obesity and cancer worldwide and the proven causal relationship between these diseases, it is necessary to intensify nutrition education and promote a healthy lifestyle in order to minimize excessive body weight, and thus reduce the incidence of cancer.

Low intensity pulsed ultrasound reduces liver inflammation caused by fatigue exercise.

Low-intensity pulsed ultrasound (LIPUS) has been shown to have many benefits, such as inhibiting inflammation, stimulating cell proliferation and differentiation, promoting angiogenesis, and so on. So, can exercise fatigue induced liver inflammation be effectively relieved by LIPUS? If possible, what is the possible mechanism? This study first investigated the effect of different intensity exercise on liver inflammation. Rats were divided into three groups: normal control group, exercise fatigue group, and aerobic exercise group. The results showed that aerobic exercise increases both anti-inflammatory factors and pro-inflammatory factors, while fatigue exercise decreases anti-inflammatory factors and increases pro-inflammatory factors, leading to severe liver injury and fibrosis. Then, we investigated the therapeutic effect of LIPUS on liver inflammation caused by exercise fatigue. Starting from the 6th week, the liver was irradiated with LIPUS of 80 mW/cm2 for 20 min/d after daily exercise for 7 weeks. The results showed that LIPUS significantly decreased liver injury and fibrosis, significantly up-regulated the expression of STAT6, IL-13, and its receptors IL-13Rα1, and down regulated the expression of NF-κBp65 in exercise fatigue rats. These results indicate that LIPUS can reduce fatigue-induced liver inflammation, and the mechanism is related to the regulation of the IL-13/STAT6/NF-κBp65 pathway.

Laser Thermo-Photobiomodulation of Bone Marrow Mesenchymal Stem Cells

We studied the effect of laser radiation of moderate intensity with a wavelength of 970 nm on the efficiency of colony formation of rat bone marrow mesenchymal stem cells (MSC) in vitro. In this case, photobimodulation and thermal heating of MSC occur simultaneously. This combined laser treatment allows increasing the number of colonies by 6 times in comparison with the control and by more than 3 times in comparison with thermal heating alone. The mechanism of such an increase is associated with combined thermal and light effects of laser radiation of moderate intensity, which stimulates cell proliferation. This phenomenon can be used as the basis for solving the most important task of cell transplantation, associated with the expansion of autologous stem cells and activation of their proliferative potential.

Macromolecular crowding and decellularization method increase the growth factor binding potential of cell-secreted extracellular matrices.

Recombinant growth factors are used in tissue engineering to stimulate cell proliferation, migration, and differentiation. Conventional methods of growth factor delivery for therapeutic applications employ large amounts of these bioactive cues. Effective, localized growth factor release is essential to reduce the required dose and potential deleterious effects. The endogenous extracellular matrix (ECM) sequesters native growth factors through its negatively charged sulfated glycosaminoglycans. Mesenchymal stromal cells secrete an instructive extracellular matrix that can be tuned by varying culture and decellularization methods. In this study, mesenchymal stromal cell-secreted extracellular matrix was modified using λ-carrageenan as a macromolecular crowding (MMC) agent and decellularized with DNase as an alternative to previous decellularized extracellular matrices (dECM) to improve growth factor retention. Macromolecular crowding decellularized extracellular matrix contained 7.7-fold more sulfated glycosaminoglycans and 11.7-fold more total protein than decellularized extracellular matrix, with no significant difference in residual DNA. Endogenous BMP-2 was retained in macromolecular crowding decellularized extracellular matrix, whereas BMP-2 was not detected in other extracellular matrices. When implanted in a murine muscle pouch, we observed increased mineralized tissue formation with BMP-2-adsorbed macromolecular crowding decellularized extracellular matrix in vivo compared to conventional decellularized extracellular matrix. This study demonstrates the importance of decellularization method to retain endogenous sulfated glycosaminoglycans in decellularized extracellular matrix and highlights the utility of macromolecular crowding to upregulate sulfated glycosaminoglycan content. This platform has the potential to aid in the delivery of lower doses of BMP-2 or other heparin-binding growth factors in a tunable manner.

Gubentongluo decoction alleviates NLRP3 inflammasome in IgAN cell model

Immunoglobulin A nephropathy (IgAN), the most common primary renal disease, is characterized by abnormal IgA1 deposition. IgAN is caused by NOD-like receptor pyrin domain-containing-3 (NLRP3), which regulates innate immunity. Gubentongluo (GB) decoction, a traditional Chinese medicine, is an effective clinical treatment for IgAN in China. However, little is known about the underlying mechanisms. In this study, IgA1, which is separated from patients with IgAN, together with GB decoction was applied to treat human mesangial cells (HMCs). CCK-8 and the enzyme-linked immunosorbent assay were used to assess cell proliferation and the production of interleukin-1β (IL-1β), respectively. qPCR and Western blot were applied to detect the expression levels of NLRP3, IL-1β, and caspase-1. Our results showed that GB decoction inhibited IgA1-induced cell proliferation and IL-1β production. Furthermore, IgA1-induced upregulation of IL-1β, NLRP3, and caspase-1 was reduced after treatment with GB. Interestingly, MCC950, an NLRP3 inhibitor, showed similar effect as GB decoction. Additionally, NLRP3 overexpression stimulated cell proliferation, IL-1β secretion, and the expressions of IL-1β and caspase-1 in HMCs. But these effects could be alleviated by GB decoction. In conclusion, GB may play a protective role in IgAN cell model by inhibiting NLRP3.

Antimicrobial Peptide Pt5‐1c Promotes Keratinocyte Migration and Proliferation via EGFR‐mediated Akt/MAPK/STAT3 pathways

AbstractKeratinocytes, as the most dominant cell type in the epidermis, play multiple roles in skin wound healing. Recently, we have shown that a short antimicrobial peptide Pt5‐1c can promote skin wound healing via enhancing fibroblast proliferation and migration in vitro, and accelerating re‐epithelialization of murine dermal wounds in vivo.[1] However, its effects on keratinocytes is unknown. Here we clearly showed that Pt5‐1c markedly enhanced keratinocyte migration and proliferation. Moreover, Pt5‐1c stimulated keratinocyte activation by inducing the phosphorylation of epidermal growth factor receptor (EGFR), Akt, extracellular signal‐regulated kinase (ERK), p38, and signal transducer and activator of transcription 3 (STAT3) in keratinocytes. Importantly, Pt5‐1c also increased collagen production, stimulated cell proliferation, and enhanced the phosphorylation of Akt, p38 and STAT3 in the wound skin tissues. These together indicate that Pt5‐1c can promote keratinocyte migration and proliferation via activation of EGFR‐mediated Akt, MAPK, and STAT3 pathways, thereby contributing to skin wound healing.

Streptococcus pneumoniae promotes lung cancer development and progression

Streptococcus pneumoniae (SP) is associated with lung cancer, yet its role in thetumorigenesis remains uncertain. Herein we find that SP attaches to lung cancer cells via binding pneumococcal surface protein C (PspC) to platelet-activating factor receptor (PAFR). Interaction between PspC and PAFR stimulates cell proliferation and activates PI3K/AKT and nuclear factor kB (NF-kB) signalingpathways, which trigger a pro-inflammatory response. Lung cancer cellsinfected with SP form larger tumors in BALB/C mice compared to untreated cells. Mice treated with tobacco carcinogen and SP develop more lung tumors and had shorter survival period than mice treated with the carcinogen alone. Mutating PspC or PAFR abolishes tumor-promoting effects of SP. Overabundance of SP is associated with the survival. SP may play a driving role in lungtumorigenesis by activating PI3K/AKT and NF-kB pathways via binding PspC to PAFR and provide a microbial target for diagnosis and treatment of the disease.

Ingestible capsules carrying 3D printed springs: a possible future prospective for SBS treatment?

Background Short Bowel Syndrome (SBS) is a malabsorption syndrome characterised by a severe reduction of the absorbent surface of the intestinal mucosa. Treatment of this condition needs multi-professional teams and different therapies, which are not always enough to ensure enteral autonomy. New techniques are being explored, particularly distraction enterogenesis, which can allow the lengthening of the residual intestines of these patients. This study aims to demonstrate the possibility of using biodegradable materials to design ingestible capsules which carry 3D-printed springs capable of reaching the patient’s intestine. These devices could be used as a slightly invasive distraction enterogenesis technique, stimulating cell proliferation and intestinal elongation without surgery. Materials and methods Capsules were realised with gelatin from pigskin type A from Sigma-Aldrich mixed with regenerated silk fibroin (RS) obtained by reverse engineering on Bombyx Mori cocoons. Springs are composed of a structure of regenerated silk (RS) modified with graphene nanoplatelets (GNP) externally covered with a biodegradable polyhydroxybutyrate-valerate (PHBV) shell. Springs were realised with 3D printing, through which, with an extruder, PHBV and RS compounds are deposited simultaneously in a 3D structure. The springs’ capsules were then analysed with solvents simulating the gastric and intestinal environment to verify their resistance to degradation. PBS (Phosphate Buffered Saline), composed of calcium chloride and magnesium chloride (CaCl 2 + MgCl 2 ), with a pH value of 7.4, was used as a degradative agent; for the gastric tract, we chose the acetic acid, CH 3 COOH, at 12% with a pH value of 2.3. Results While the gelatin-only capsules showed poor resistance to degradation in PBS, the new compound based on gelatin and regenerated silk showed excellent resistance in gastric and intestinal environments, allowing the pills to reach the intestine without dissolving. In addition, the results show variability in the release times of the springs as a function of the pH values and the elastic constants of the springs used: the latter determined that in acetic acid, the release time is increased at an increase of the elastic constant. In contrast, in PBS, an opposite trend was observed. Conclusions Our results confirm the possibility of using gelatin, silk fibroin and PHBV to design devices capable of transporting implantable endoluminal 3D structures, drugs, or growth factors, laying the foundations for a new approach to distraction enterogenesis in SBS patients.

Discovery of a selective TC-PTP degrader for cancer immunotherapy.

T-cell protein tyrosine phosphatase (TC-PTP), encoded by PTPN2, has emerged as a promising target for cancer immunotherapy. TC-PTP deletion in B16 melanoma cells promotes tumor cell antigen presentation, while loss of TC-PTP in T-cells enhances T-cell receptor (TCR) signaling and stimulates cell proliferation and activation. Therefore, there is keen interest in developing TC-PTP inhibitors as novel immunotherapeutic agents. Through rational design and systematic screening, we discovered the first highly potent and selective TC-PTP PROTAC degrader, TP1L, which induces degradation of TC-PTP in multiple cell lines with low nanomolar DC50s and >110-fold selectivity over the closely related PTP1B. TP1L elevates the phosphorylation level of TC-PTP substrates including pSTAT1 and pJAK1, while pJAK2, the substrate of PTP1B, is unaffected by the TC-PTP degrader. TP1L also intensifies interferon gamma (IFN-γ) signaling and increases MHC-I expression. In Jurkat cells, TP1L activates TCR signaling through increased phosphorylation of LCK. Furthermore, in a CAR-T cell and KB tumor cell co-culture model, TP1L enhances CAR-T cell mediated tumor killing efficacy through activation of the CAR-T cells. Thus, we surmise that TP1L not only provides a unique opportunity for in-depth interrogation of TC-PTP biology but also serves as an excellent starting point for the development of novel immunotherapeutic agents targeting TC-PTP.

Overlapping Actions of L-Thyroxine (T4) and Steroids in Breast Cancer Cells: Mediation by Cell Surface Integrin αvβ3

The overlap of actions of nonpeptide small endocrine molecules—thyroid hormone and steroids—include two panels of actions. One set is initiated at the nuclear receptors for these hormones and a second set of actions for both hormones is initiated at the extracellular domain of plasma membrane integrin αvβ3. This brief review is concerned with integrin-based receptors on breast cancer cells. On such cells, thyroid hormone as L-thyroxine (T4) at physiological concentrations can stimulate proliferation of breast cancer cells via the thyroid hormone analogue receptor on αvβ3 and, in the absence of estrogen, via the nuclear estrogen receptor-α (ER α). Such observations emphasize the postmenopausal relevance of nuclear estrogen receptor. The deaminated T4 derivative, tetraiodothyroacetic acid (tetrac), blocks T4 actions at the integrin. An androgen receptor on the integrin mediates stimulation of breast cancer cell proliferation by dihydrotestosterone (DHT). T4 controls the activation state of the integrin, a factor that may determine the accessibility of the androgen receptor on αvβ3 to DHT and thus to DHT-driven cell proliferation. An estrogen receptor appears to be present on the integrin, but its functions have not been defined. It is not yet known whether tetrac alters function of the steroid receptors that are adjacent to the T4 binding site on αvβ3. The overlap of T4 and steroid functions in breast cancer cells may offer additional options for clinical management of this type of cancer.

Abnormal expression of long non-coding RNA FGD5-AS1 affects the development of ovarian cancer through regulating miR-107/RBBP6 axis.

Long non-coding RNAs (lncRNAs) are important players in cancer development. LncRNA FGD5-AS1 has been reported as a potential oncogene in ovarian cancer (OC). The present paper focused on the action mechanism of FGD5-AS1 in OC. Clinical OC samples were collected for expression analyses of FGD5-AS1, RBBP6, and miR-107. The expression of FGD5-AS1, RBBP6, and miR-107 in OC cells was altered by transfection. OC cell proliferation was assessed by MTT and colony formation assays, and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with OC cell supernatants by matrigel angiogenesis assay. The interactions among FGD5-AS1, miR-107, and RBBP6 were detected by luciferase reporter assay. FGD5-AS1 and RBBP6 were strongly expressed and miR-107 was poorly expressed in clinical OC samples and OC cell lines. FGD5-AS1 or RBBP6 overexpression in Hey and SKOV3 cells could potentiate OC cell proliferation and HUVEC angiogenesis, while FGD5-AS1 or RBBP6 knockdown in OC cells inhibited the above cellular processes. FGD5-AS1 targeted miR-107 to positively regulate RBBP6 expression. Additionally, miR-107 overexpression or RBBP6 knockdown in SKOV3 cells partially reversed the FGD5-AS1-dependent stimulation of OC cell proliferation and HUVEC angiogenesis. FGD5-AS1 may act as a promoter of OC via miR-107/RBBP6 axis.

Silk fibroin-based piezoelectric nanofibrous scaffolds for rapid wound healing.

Piezoelectric polymer nanofibers are attracting increasing attention in the stimulation of cell growth and proliferation in tissue engineering and wound healing applications. However, their intrinsic non-biodegradability in vivo hinders widespread applications in the biological fields. Herein, we designed, synthesized and characterized composite materials of silk fibroin (SF)/LiNbO3 (LN) nanoparticles/MWCNTs by electrospinning technology, which displayed good biocompatibility and comparable piezoelectric properties with an output current of up to 15 nA and output voltage of up to 0.6 V under pressure stimulation, remaining stable after 200 cycles of pressure release without significant decay. Meanwhile, the mechanical properties of the LN/CNTs/SF-nanofiber scaffolds (SF-NFSs) are also enhanced, with a tensile strength reaching 12.84 MPa and an elongation at break reaching 80.07%. Importantly, in vitro cell proliferation experiments showed that the LN/CNTs/SF-NFSs promoted cell proliferation at a rate of 43%. Accordingly, the mouse wound healing experiments further indicated that they could accelerate the healing of skin wounds in mice that were continuously moving. Therefore, SF-based piezoelectric nanofibrous scaffolds exhibit potential for use in rapid wound healing and this sheds light on smart treatment for tissue engineering in biomedicine.

Hyper-Aggressiveness of Bystander Cells in an Anti-Tumor Photodynamic Therapy Model: Role of Nitric Oxide Produced by Targeted Cells.

When selected tumor cells in a large in vitro population are exposed to ionizing radiation, they can send pro-survival signals to non-exposed counterparts (bystander cells). If there is no physical contact between irradiated and bystander cells, the latter respond to mediators from targeted cells that diffuse through the medium. One such mediator is known to be nitric oxide (NO). It was recently discovered that non-ionizing anti-tumor photodynamic therapy (PDT) can also elicit pro-survival/expansion bystander effects in a variety of human cancer cells. A novel silicone ring-based approach was used for distinguishing photodynamically-targeted cells from non-targeted bystanders. A key finding was that NO from upregulated iNOS in surviving targeted cells diffused to the bystanders and caused iNOS/NO upregulation there, which in turn stimulated cell proliferation and migration. The intensity of these responses depended on the extent of iNOS/NO induction in targeted cells of different cancer lines. Moreover, the responses could be replicated using NO from the chemical donor DETA/NO. This review will focus on these and related findings, their negative implications for clinical PDT, and how these might be averted by using pharmacologic inhibitors of iNOS activity or transcription.

TBX3 stimulates proliferation and stem cell self-renewal in bladder carcinoma.

With the change of people's lifestyle in recent years, bladder carcinoma has been the second leading cause of death for men. Nevertheless, surgical results of bladder carcinoma are unsatisfying with recurrence and distant metastasis. Therefore, it is urgent to find a new target for bladder carcinoma treatment. The protein and mRNA expression levels of TBX3 in bladder carcinoma tissue samples and cells were tested using western blot and qRT-PCR assays, respectively. Cancer stem cells (CSCs) were separated with immunomagnetic beads. Expression levels of cell stemness-associated proteins CD44, CD24 and ESA in T24 CSCs and T24 cells were detected by western blot assay. Cell self-renewal ability was detected by stem cell sphere formation assay. CCK-8 and colony formation assays examined cell viability and proliferation. Cell apoptotic level was examined by flow cytometry. Elevated TBX3 expression in bladder carcinoma stimulated cell proliferation and inhibited cell apoptosis. Stemness-related proteins and TBX3 were highly expressed in T24 CSCs relative to those in normal bladder carcinoma cells. In addition, TBX3 promoted stem cell self-renewal and inhibited cell apoptosis. Finally, qRT-PCR, western blot and cell sphere formation assays revealed that the potential role of TGF-β1 in the regulation of TBX3. TBX3, mediated by TGF-β1, can promote bladder carcinoma cell proliferation, inhibit apoptosis, and enhance cell stemness. Hence, TBX3 is a potential target to stem cells of bladder carcinoma.

Evaluation of Growth Hormone’s Effects on the Activation of Monocyte Cell Line THP-1 and U937

Growth hormone (GH) is a peptide hormone secreted by the pituitary gland and stimulates cell proliferation and division to promote tissue growth. In addition, the development of the immune system and the regulation of the immune response have been reported. Along with the research results related to the inflammatory control function, a correlation between the severe symptoms of COVID-19 in the elderly and a decrease in the secretion of growth hormone has recently been suggested. Therefore, this research team studied the effect of growth hormone on the proliferation and inflammatory cytokine secretion of monocyte cell lines THP-1 and U937. As a result, it was confirmed that the proliferation of THP-1 and the secretion of TNF-α and IL-1β induced by LPS were decreased by growth hormone. On the other hand, the proliferation of U937 cell line was increased by growth hormone treatment, whereas the secretion of TNF-α and IL-1β was hardly affected. In the future, the analysis of the GH receptors expressed by the two cell lines and the study of the molecular mechanism of GH action are required. In addition, it is considered that the cell stimulation technique using Poly(I:C) needs to be established more accurately.