Current status of cancer starvation therapy.

Conventional therapies for malignant tumors have limitations and disadvantages. In recent years, the cancer starvation therapy has emerged which intends to deprive cancer cells of nutritional supply. There are several approaches to"starve" cancer cells: to intervene tumor angiogenesis by targeted inhibition of angiogenic factors or their receptors and integrins; to block the blood supply of cancer cells by embolizing or compressing blood vessels; to intervene metabolic process of cancer cells by inhibition of the signal pathways of mitochondrial serine-glycine-one earbon metabolism, glycolysis and amino acid metabolism; cancer starvation therapy can be employed with oxidation therapy, chemotherapy, sonodynamic therapy, anti-autophagy therapy or other therapies to achieve synergistic effects. This article reviews the research progress of cancer starvation therapy in recent years and discusses the existing problems.

Inhibition of integrin ß3, a binding partner of kallistatin, leads to reduced viability, invasion and proliferation in NCI-H446 cells.

BACKGROUND: Kallistatin is a serine proteinase inhibitor and heparin-binding protein. It is considered an endogenous angiogenic inhibitor. In addition, multiple studies demonstrated that kallistatin directly inhibits cancer cell growth. However, the molecular mechanisms underlying these effects remain unclear. METHODS: Pull-down, immunoprecipitation, and immunoblotting were used for binding experiments. To elucidate the mechanisms, integrin ß3 knockdown (siRNA) or blockage (antibody treatment) on the cell surface of small the cell lung cancer NCI-H446 cell line was used. RESULTS: Interestingly, kallistatin was capable of binding integrin ß3 on the cell surface of NCI-H446 cells. Meanwhile, integrin ß3 knockdown or blockage resulted in loss of antitumor activities induced by kallistatin. Furthermore, kallistatin suppressed tyrosine phosphorylation of integrin ß3 and its downstream signaling pathways, including FAK/-Src, AKT and Erk/MAPK. Viability, proliferation and migration of NCI-H446 cells were inhibited by kallistatin, with Bcl-2 and Grb2 downregulation, and Bax, cleaved caspase-9 and caspase 3 upregulation. CONCLUSIONS: These findings reveal a novel role for kallistatin in preventing small cell lung cancer growth and mobility, by direct interaction with integrin ß3, leading to blockade of the related signaling pathway.

Two novel phenanthraquinones with anti-cancer activity isolated from Bletilla striata.

7-Hydroxy-2-methoxy-phenanthrene-3,4-dione and 3',7',7-trihydroxy-2,2',4'-trimethoxy-[1,8'-biphenanthrene]-3,4-dione, two novel compounds and four known compounds were isolated from Bletilla striata. The structures of the compounds were established on the basis of extensive spectroscopic analysis. The two compounds exhibited antiproliferative effects using the MTT test; these effects may be due to cell cycle arrest and inducing ROS generation.

Biological Evaluation of Ferrocenyl Olefins: Cancer Cell Growth Inhibition, ROS Production, and Apoptosis Activity.

The antiproliferative effects of various ferrocenyl olefins were evaluated against the cell lines MCF-7 (human breast cancer cells), DLD-1 (human colon adenocarcinoma cells), HUVEC (human umbilical vein endothelial cells), and A549 (human lung carcinoma cells), using the MTT test. IC50 values were determined. Compounds 8, 9, 11, and 12 with high antiproliferative activity were tested for their reactive oxygen species (ROS) production, and cell cycle analysis was performed on A549 cells. The results show that these compounds might perform their antiproliferative activity through inducing ROS generation, apoptosis induction, and cell cycle arrest.

[Advanced technologies in semen stain identification].

Semen stain identification is one of the crucial tasks for collection of criminal evidence by forensic techniques. Substances such as DNA and RNA contained in semen stains can serve as a source of personalized evidence targeting the suspect. Therefore, semen stain identification is vital to inferring the case attributes and the facts of the crime. The conventional methods of forensic stain identification focus on the detection of specific-function protein and/or high-content protein, such as alkaline phosphatase and PSA. Although the specificity of such protein markers is relatively high, these methods yield a limited rate of success for several factors, including poor stability, low sensitivity of the target protein, and possible subjectivity of the performer. In order to overcome these limitations, new technologies such as Raman spectroscopy, mass spectrometry for protein markers, sperm-specific aptamer, mRNA, microRNA, and DNA methylation assays have been studied and recommended by many investigators. These new technologies are paving a new ground for personalized trace analysis and even for detection of over-timed specimens.

Neuroprotection by saponins.

Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones. Their diverse biological activities are ascribed to their different structures. Saponins have long been recognized as key ingredients in traditional Chinese medicine. Accumulated evidence suggests that saponins have significant neuroprotective effects on attenuation of central nervous system disorders, such as stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, our understanding of the mechanisms underlying the observed effects remains incomplete. Based on recently reported data from basic and clinical studies, this review highlights the proposed mechanisms of their neuroprotective function including antioxidant, modulation of neurotransmitters, anti-apoptosis, anti-inflammation, attenuating Ca(2+) influx, modulating neurotrophic factors, inhibiting tau phosphorylation, and regeneration of neural networks.

[The effect of Connexin43 downregulation on biological functions of HUVEC].

Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA (siRNA) to reduce the expression of connexin43 in human umbilical vein endothelial cell (HUVEC), and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by -80% in HUVEC (P < 0.05), and decreased the intercellular communication by -65% (P < 0.05). The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly (P < 0.05), compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.

[Ribozyme riboswitch based gene expression regulation systems for gene therapy applications: progress and challenges].

Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.

Cytotoxic activity of the alkaloids from Broussonetia papyrifera fruits.

CONTEXT: Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Recently, a number of compounds with biological and pharmacological activities have been extracted from the plant and used as chemotherapeutic candidates to treat a range of diseases such as cancer. OBJECTIVE: The current study was designed to isolate the alkaloid compounds from ethyl acetate extraction of Broussonetia papyrifera fruits, and to evaluate the cytotoxic activity of total alkaloids as well as individual isoquinoline alkaloids from B. papyrifera fruits. METHODS: Alkaloid compounds were isolated from the ethyl acetate extraction by silica gel column chromatography methods using CHCl3/MeOH as eluents. The compounds' structures were determined by detailed analysis of NMR, MS spectral data, and chemical methodology. Cytotoxic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods against human A375, Hela, BEL-7402 cancer cells, and non-cancer cells. RESULTS: Two isoquinonline alkaloids were isolated and characterized as N-norchelerythrine and dihydrosanguinarine. The total alkaloids and seven individual alkaloids had higher activities on BEL-7402 and Hela cell lines with low IC50 values 6.61-47.41 and 5.97-40.17 µg/mL (<50 µg/mL). Nitidine, broussonpapyrine, and chelerythrine had strong toxic on non-cancer cells with IC50 value 18.01, 19.91, and 22.31 µg/mL, respectively. DISCUSSION: N-Norchelerythrine and dihydrosanguinarine were isolated from this plant for the first time. Our data implicated that seven isoquinoline alkaloids had cytotoxity with structure-activity relationships, which provided fundamental information for further modification of their anticancer effect.

Macroporous Directed and Interconnected Carbon Architectures Endow Amorphous Silicon Nanodots as Low-Strain and Fast-Charging Anode for Lithium-Ion Batteries.

Fabricating low-strain and fast-charging silicon-carbon composite anodes is highly desired but remains a huge challenge for lithium-ion batteries. Herein, we report a unique silicon-carbon composite fabricated by uniformly dispersing amorphous Si nanodots (SiNDs) in carbon nanospheres (SiNDs/C) that are welded on the wall of the macroporous carbon framework (MPCF) by vertical graphene (VG), labeled as MPCF@VG@SiNDs/C. The high dispersity and amorphous features of ultrasmall SiNDs (~ 0.7 nm), the flexible and directed electron/Li+ transport channels of VG, and the MPCF impart the MPCF@VG@SiNDs/C more lithium storage sites, rapid Li+ transport path, and unique low-strain property during Li+ storage. Consequently, the MPCF@VG@SiNDs/C exhibits high cycle stability (1301.4 mAh g-1 at 1 A g-1 after 1000 cycles without apparent decay) and high rate capacity (910.3 mAh g-1, 20 A g-1) in half cells based on industrial electrode standards. The assembled pouch full cell delivers a high energy density (1694.0 Wh L-1; 602.8 Wh kg-1) and an excellent fast-charging capability (498.5 Wh kg-1, charging for 16.8 min at 3 C). This study opens new possibilities for preparing advanced silicon-carbon composite anodes for practical applications.

Adhesive, Flexible, and Fast Degradable 3D-Printed Wound Dressings with a Simple Composition.

3D printing technology has revolutionized the field of wound dressings, offering tailored solutions with mechanical support to facilitate wound closure. In addition to personalization, the intricate nature of the wound healing process requires wound dressing materials with diverse properties, such as moisturization, flexibility, adhesion, anti-oxidation and degradability. Unfortunately, current materials used in digital light processing (DLP) 3D printing have been inadequate in meeting these crucial criteria. This study introduces a novel DLP resin that is biocompatible and consists of only three commonly employed non-toxic compounds in biomaterials, that is, dopamine, poly(ethylene glycol) diacrylate, and N-vinylpyrrolidone. Simple as it is, this material system fulfills all essential functions for effective wound healing. Unlike most DLP resins that are non-degradable and rigid, this material exhibits tunable and rapid degradation kinetics, allowing for complete hydrolysis within a few hours. Furthermore, the high flexibility enables conformal application of complex dressings in challenging areas such as finger joints. Using a difficult-to-heal wound model, the manifold positive effects on wound healing in vivo, including granulation tissue formation, inflammation regulation, and vascularization are substantiated. The simplicity and versatility of this material make it a promising option for personalized wound care, holding significant potential for future translation.

[Recent progress of the aptamer-based antiviral drugs].

Aptamers are capable of binding a wide range of biomolecular targets with high affinity and specificity. It has been widely developed for diagnostic and therapeutic purposes. Because of unique three dimensional structures and cell-membrane penetration, aptamers inhibit virus infection not only through binding specific target, such as the viral envelope, genomic site, enzyme, or other viral components, but also can be connected to each other or with siRNA jointly achieve antiviral activity. Taking human immunodeficiency virus and hepatitis C virus as examples, this paper reviewed the effects and mechanisms of aptamers on disturbing viral infection and replication steps. It may provide an insight to the development of aptamer-based new antiviral drugs.

Discovery of fecal microbial signatures in patients with ankylosing spondylitis.

Objectives: This study aimed to investigate the characteristics of the gut microbiota in Chinese patients with ankylosing spondylitis (AS) and healthy controls in Quanzhou aiming to explore the correlation between microbiome changes and AS activities. Patients and methods: In this study, high-throughput sequencing of the gene of 16S ribosomal RNA (16S rRNA) in fecal samples from 40 AS patients and 40 healthy controls, for a total of 80 participants (70 males, 10 females; mean age 33.7±10.7 years; range, 15 to 58 years), was conducted between January 2018 and January 2019. Alpha and beta diversity were analyzed using the QIIME (Quantitative Insights Into Microbial Ecology) software, and differences were analyzed using Student's t-test, linear discriminant analysis coupled with effect size and Metastats. Finally, a correlation network was constructed using Pearson's analysis. Results: The alpha index values of the AS group were not significantly different from those of the control group. At the genus level, eight genera, Ruminiclostridium_9, Fusicatenibacter, Adlercreutzia, CAG-56, Intestinimonas, Lachnospira, Bacteroides, and Pseudoflavonifractor, were significantly enriched in patients with AS, whereas the abundance of uncultured_bacterium_f_Saccharimonadaceae, Prevotella_7, uncultured_bacterium_f_ Enterobacteriaceae, Cronobacter, Prevotellaceae_NK3B31_group, and Weissella were significantly decreased in patients with AS. In addition, diseaserelated gut microbial communities were detected in patients with AS. Conclusion: We found differences in the gut microbiome between the patients with AS and controls and identified potential disease activity-related bacterial communities.

[The molecular design and drug development of recombinant long-acting follicle stimulating hormone].

Follicle-stimulating hormone (FSH) is a glycoprotein which regulates the development, growth, pubertal maturation and reproductive processes of the body. Exogenous FSH has been used to promote ovarian follicular growth and maturation in female and spermatogenesis in male. The relative short elimination half life and rapid metabolic clearance of current versions of FSH require a daily or twice-daily scheduled subcutaneous injection to maintain stable FSH level being not below the threshold during ovarian stimulation. The development of recombinant long-acting FSH with enhanced biological activities may be helpful for less injection therefore to improve patient compliance, while reducing patient stress and error rates. A number of technological strategies have been explored to develop recombinant longer-acting FSH. For examples, attachment of the C-terminal peptide (CTP) of the human chorionic gonadotropin beta subunit or a sequence containing potential glycosylation sites to either subunit of FSH, creation of a single chain containing the alpha and beta subunits of FSH combined with CTP or N-linked glycosylation signal sequence as a linker, or fusion of the Fc domain of IgGi to FSH. Based on the modifiable molecular structure and pharmacokinetic and pharmacodynamic properties of recombinant FSH, it is hopeful that more FSH drugs with prolonged half-life and increased bioactivity will be developed to meet the modern clinical demands.

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer.

Purpose: The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods: Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results: mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion: Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.

Efficacy of needle-knife combined with etanercept treatment regarding disease activity and hip joint function in ankylosing spondylitis patients with hip joint involvement: A randomized controlled study.

This study aimed to assess the efficacy of needle-knife (NK) combined with etanercept (NKCE) in attenuating pain, inflammation, disease activity, and improving hip joint function in ankylosing spondylitis (AS) patients with hip joint involvement.Totally, 90 patients with active AS involving unilateral hip joint were enrolled and randomly assigned in 1:1:1 ratio to receive NKCE, NK or conventional drugs (control). The ESR, CRP, hip joint pain Visual Analogue Scale (VAS) score, bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI), modified Harris hip score (mHHS), and range of motion (ROM) of affected hip joint were assessed at baseline (W0), after 1-week treatment (W1) and after 24-week treatment (W24).ESR and CRP were decreased in NKCE group compared with NK and control groups, while was not attenuated in NK group compared with control group. Regrading pain and disease activity, NKCE group presented a reduction in hip pain VAS score and BASDAI compared with NK and control groups, and NK group showed a decrease in hip pain VAS score and BASDAI compared with control group. Besides, BASFI was lowered in NKCE and NK groups compared with control group, but similar between NKCE and NK groups. mHHS and hip ROM were raised in NKCE and NK groups compared with control group, but similar between NKCE and NK groups.NKCE decreases hip pain, inflammation, disease activity and improves hip joint function in AS patients with hip joint involvement.

Actions of fibroblast growth factor-8 in bone cells in vitro.

The fibroblast growth factors (FGFs) are a group of at least 25 structurally related peptides that are involved in many biological processes. Some FGFs are active in bone, including FGF-1, FGF-2, and FGF-18, and recent evidence indicates that FGF-8 is osteogenic, particularly in mesenchymal stem cells. In the current study, we found that FGF-8 was expressed in rat primary osteoblasts and in osteoblastic UMR-106 and MC3T3-E1 cells. Both FGF-8a and FGF-8b potently stimulated the proliferation of osteoblastic cells, whereas they inhibited the formation of mineralized bone nodules in long-term cultures of osteoblasts and reduced the levels of osteoblast differentiation markers, osteocalcin, and bone sialoprotein. FGF-8a induced the phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) in osteoblastic cells; however, its mitogenic actions were not blocked by either the MAPK kinase (MEK) inhibitor U-0126 or the PI 3-kinase (PI3K) inhibitor LY-294002. Interestingly, FGF-8a, unlike FGF-8b and other members of the family, inhibited osteoclastogenesis in mouse bone marrow cultures, and this was via a receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG)-independent manner. However, FGF-8a did not affect osteoclastogenesis in RAW 264.7 cells (a macrophage cell line devoid of stromal cells) exogenously stimulated by RANKL, nor did it affect mature osteoclast function as assessed in rat calvarial organ cultures and isolated mature osteoclasts. In summary, we have demonstrated that FGF-8 is active in bone cells, stimulating osteoblast proliferation in a MAPK-independent pathway and inhibiting osteoclastogenesis via a RANKL/OPG-independent mechanism. These data suggest that FGF-8 may have a physiological role in bone acting in an autocrine/paracrine manner.

Hybrid hollow spheres of carbon@CoxNi1-xMoO4 as advanced electrodes for high-performance asymmetric supercapacitors.

Combining pseudocapacitive materials with conductive substrates is an effective approach to enhance the overall performance of electrodes for supercapacitors. Herein, NiMoO4 nanosheets were grown on the surface of porous carbon nanospheres (PCNS) that were derived from cyclodextrin, resulting in PCNS@NiMoO4 hollow nanospheres. Co was further doped into NiMoO4 which gave rise to a composite PCNS@CoxNi1-xMoO4. The capacitive performance of these materials was systematically examined. Compared with pure NiMoO4 and PCNS@NiMoO4, PCNS@Co0.21Ni0.79MoO4 showed the highest specific capacitance of 954 F g-1 at 1 A g-1 and an extraordinary rate performance of 92.8% retention at 40 A g-1, which are significantly higher than those of PCNS@NiMoO4 and pure NiMoO4. This enhancement was due to the fact that PCNS provides high electrical conductivity, the hollow structure enables excellent contact and facile penetration of the electrolyte into the active material, and Co doping further improves the electrical conductivity and provides extra redox reaction sites. By using PCNS@Co0.21Ni0.79MoO4 as the positive electrode and activated carbon (AC) as the negative electrode, an asymmetric supercapacitor was fabricated. Such a device delivered an energy density of 36.7 W h kg-1 at a power density of 346.4 W kg-1, and an outstanding cycling stability with 90.2% retention of its initial capacitance after 5000 cycles of charge and discharge.

Two-dimensional hierarchically porous carbon nanosheets for flexible aqueous supercapacitors with high volumetric capacitance.

Two-dimensional carbon nanomaterials can be assembled into a dense film and used for flexible supercapacitors, but the high packing density leads to restacking problems and poor volumetric capacitance. To address this challenge, we report two-dimensional hierarchically porous carbon (2D-HPC) consisting of micro-, meso-, and macro-pores on the 2D sheet, which shows superior capacitance and rate capability compared with a 2D carbon nanosheet consisting predominantly of micro-pores. A flexible supercapacitor fabricated with the 2D-HPC presents a high volumetric capacitance of 412 F cm-3, a high volumetric energy density of 9.2 mW h cm-3 and a power density of 120 mW cm-3.

miR-106b-5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3.

BACKGROUND AND OBJECTIVES: The roles of microRNA(miR)-106b-5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR-106b-5p expression in HCC and its underlying mechanisms. METHODS: Expression levels of miR-106b-5p in 108 HCC clinical samples by quantitative real-time reverse transcription PCR. Associations of miR-106b-5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi-square test, Kaplan-Meier, and Cox proportional regression analyses, respectively. The target gene of miR-106b-5p and their functions in HCC cells were investigated by luciferase reporter, CCK-8, and Transwell Matrigel invasion assays. RESULTS: miR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals. Importantly, miR-106b-5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR-106b-5p in HCC cells. Functionally, miR-106b-5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR-106b-5p overexpression. CONCLUSIONS: miR-106b-5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR-106b-5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.