Two-way Regulation Research Articles

A DNA damage-amplifying nanoagent for cancer treatment via two-way regulation of redox dyshomeostasis and downregulation of tetrahydrofolate

DNA damage-based therapy is widely used in cancer treatment, yet its therapeutic efficacy is constrained by the redox homeostasis and DNA damage repair mechanisms of tumor cells. To address these limitations and enhance the efficacy of DNA damage-based therapy, HA-CuH@MTX, a copper-histidine metal-organic complex (CuH) loaded with methotrexate (MTX) and modified with hyaluronic acid (HA), was developed to amplify the DNA damage induced. In vitro experiments demonstrated that the presence of both Cu+ and Cu2+ in HA-CuH@MTX enables two-way regulated redox dyshomeostasis (RDH), achieved through Cu+-catalyzed generation of •OH and Cu2+-mediated consumption of glutathione, thereby facilitating efficient DNA oxidative damage. In addition, DNA damage repair is synergistically inhibited by impairing nucleotide synthesis via histidine metabolism and MTX downregulation of tetrahydrofolate, a crucial raw material in nucleotide synthesis. In vivo experiments with 4T1 tumor-bearing mice demonstrate 83.6 % inhibition of tumor growth by HA-CuH@MTX. This work provides a new strategy to amplify the DNA damage caused by DNA damage-based cancer therapies, and holds great potential for improving their therapeutic efficacy.

Nano-Regulator Inhibits Tumor Immune Escape via the "Two-Way Regulation" Epigenetic Therapy Strategy.

Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint-dependent suppression limits the immunotherapeutic effect. Herein, a "two-way regulation" epigenetic therapeutic strategy is proposed using a novel nano-regulator that inhibits tumor immune escape by upregulating expression of tumor-associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD-L1) expression to block programmed death-1 (PD-1)/PD-L1. To engineer the nano-regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 are co-loaded into the cationic liposomes with condensing the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine (CpG) via electrostatic interactions to obtain G-J/ZL. Then, asparagine-glycine-arginine (NGR) modified material carboxymethyl-chitosan (CMCS) is coated on the surface of G-J/ZL to construct CG-J/ZL. CG-J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD-L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour-associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano-regulator CG-J/ZL can upregulate TAAs expression to enhance T-cell infiltration and downregulate PD-L1 expression to improve the recognition of tumor cells by T-cells, representing a promising strategy to improve antitumor immune response.

Research progress on rheumatoid arthritis-associated depression.

Depression is an independent mood disorder and one of the most common comorbidities of rheumatoid arthritis (RA). Growing evidence suggests that there is two-way regulation between RA and depression, resulting in a vicious cycle of RA, depression, poor outcomes, and disease burden. The rising prevalence of RA-associated depression warrants a re-examination of the relationships between them. Here we provide an overview of the etiology and pathological mechanisms of RA-associated depression, and recent advances in treatment with biologics, which will facilitate the development of new and effective prevention and treatment strategies.

A Complete Information Interaction-Based Bus Passenger Flow Control Model for Epidemic Spread Prevention

Because the strategy of stopping bus lines during an epidemic can negatively impact residents, this study proposes a bus passenger flow control model to optimize the safety of and access to bus transport. The information interaction environment can provide a means for the two-way regulation of buses and passengers. In this model, passengers first request their pick-up and drop-off location, and then the bus feeds back information on whether it accepts the request. Through this method, passenger flow control can be realized through complete information interaction. The study aimed to establish a multi-objective function that minimizes the weighted total cost of the safety cost, the passenger travel cost, and the bus travel cost during an epidemic. The constraints were the full load and riding rates of urban buses in peak periods under the condition of epidemic prevention and control. The results showed that, in the morning peak period, the passenger flow control scheme reduced the passenger infection probability by 17.89%, compared with no passenger flow control scheme. The weighted total cost of the epidemic safety cost, the passenger travel cost, and the bus operation cost was reduced by 8.04%. The optimization effect of the passenger flow control scheme of this model is good, and not only reduces the probability of passengers being infected, but also meets the requirements of epidemic prevention and the travel needs of residents.

EFFECT OF REGULAR PHYSICAL EXERCISE ON HUMAN IMMUNITY

ABSTRACT Introduction: A suitable combination of physical exercise and nutrition can effectively improve the body’s immunity and function. It has a positive effect and value on the healthy development of the body. Objective: To compare the immune function of athletes and non-athletes. We study the immune effect of spleen gland peptides on athletes. Methods: This study used different exercise methods, intensities, durations, and evaluated the effect of spleen peptide on the immune function of the body. Results: Physical exercise can improve human immunity. The spleen peptide directly exerts a positive two-way regulation effect on the immune function of athletes after intense and stressful exercise. Conclusion: The oral administration of spleen aminopeptidase enhances the athlete’s body fluid and cellular immune function and effectively reduces the infection rate of the athlete’s respiratory tract. Level of evidence II; Therapeutic studies - investigation of treatment results.

Methodology for monitoring soil moisture in systems of double-acting irrigation

The purpose of the research is, based on the analysis of field studies, to select a well for sampling soil moisture relative to the entire inter-drain space for monitoring double-acting irrigation systems. To solve the problem, a monitoring system on double-acting irrigation systems, providing two-way regulation of the water regime in the root layer of the soil, as well as to ensure fire safety of the entire peat profile. Based on the results of field studies on the peat bogs of the Dubna river floodplain in the Moscow Region, a representative sampling point for monitoring double-acting irrigation systems has been substantiated. The sampling point should be located on an area with the same relief, the soil profile should be uniform with the properties and soil morphology characteristic of the entire field. Wells for taking moisture samples are recommended to be installed at a distance of ¼E (E is the distance between channels), in this case the measured moisture value will be closest to the average value in relation to the entire site. For the soil conditions of the experimental site, the moisture content in the selected well during sluicing in the dry summer period increased by 1.5 times to the anti-fire moisture standard. If the water level in the canal is maintained up to 85 cm for 5 or more hours, the humidity will rise to anti-fire moisture in the dry period.

Bi-Directional Relationship Between Autophagy and Inflammasomes in Neurodegenerative Disorders.

The innate immune system, as the first line of cellular defense, triggers a protective response called inflammation when encountered with invading pathogens. Inflammasome is a multi-protein cytosolic signaling complex that induces inflammation and is critical for inflammation-induced pyroptotic cell death. Inflammasome activation has been found associated with neurodegenerative disorders (NDs), inflammatory diseases, and cancer. Autophagy is a crucial intracellular quality control and homeostasis process which removes the dysfunctional organelles, damaged proteins, and pathogens by sequestering the cytosolic components in a double-membrane vesicle, which eventually fuses with lysosome resulting in cargo degradation. Autophagy disruption has been observed in many NDs presented with persistent neuroinflammation and excessive inflammasome activation. An interplay between inflammation activation and the autophagy process has been realized over the last decade. In the case of NDs, autophagy regulates neuroinflammation load and cellular damage either by engulfing the misfolded protein deposits, dysfunctional mitochondria, or the inflammasome complex itself. A healthy two-way regulation between both cellular processes has been realized for cell survival and cell defense during inflammatory conditions. Therefore, clinical interest in the modulation of inflammasome activation by autophagy inducers is rapidly growing. In this review, we discuss the structural basis of inflammasome activation and the mechanistic ideas of the autophagy process in NDs. Along with comments on multiple ways of neuroinflammation regulation by microglial autophagy, we also present a perspective on pharmacological opportunities in this molecular interplay pertaining to NDs.

Water Supply of the Ukrainian Polesie Ecoregion Drained Areas in Modern Anthropogenic Climate Changes

Abstract The paper focuses on research on improving the water supply of drainage systems of humid areas in the context of anthropogenic climate change. The aim of the research is to elaborate on the ways for increasing the available water supply of drainage systems and restoring active water regulation on reclaimed lands in a changing climate. Reclaimed lands are the main factor of sustainable agricultural production in Ukraine and guarantors of its stability. The area of drained lands in Ukraine is about 3.2 million hectares, including 2.3 million hectares drained with the help of closed drainage; in an area of 1.3 million hectares a two-way regulation of the soil water regime is carried out. An increase in air temperature and uneven distribution of precipitation, which has a torrential, local character in the warm period, do not allow for the e ective accumulation of moisture. The recurrence of droughts in di erent justified climatic zones of Ukraine has increased by 20–40%, which prevents sustainable agricultural production in the zone of su cient atmospheric moisture, in particular the Polesie Ecoregion. In this paper, the analysis of water consumption of reclaimed lands in the Polesie Ecoregion of Ukraine is carried out, on the examples of the drainage system “Maryanivka” and the calculation of the water supply for the corn and winter wheat.

Abstract 2032: Vitamin B12 augments Ca2+ dependent cytotoxicity of diethyldithiocarbamate through excessive ER-vacuolization, oxidative stress and mitochondrial depolarization in MCF-7 cells in culture

Abstract Coordinated organization of intracellular organelles into functional networks is vital for cells. Mitochondrial and endoplasmic reticulum (ER) interaction in regulation of cell Ca2+ homeostasis is crucial for cell death and survival. Function of these intracellular organelles involved in two-way regulation of the status of major cell metabolites including protein, lipid exchange and intracellular Ca2+ homeostasis. Disulfiram and its derivatives recently attracted attention as a potential anticancer treatment (Kona et al., 2011). Combined use of hydroxycobalamin (vitamin B12b) and diethyldithiocarbamate (DDTC) demonstrated synergistic effect (combination index=0.25) and enhanced the cytotoxic effect of DDTC in number of transformed cell lines in culture (Solovieva et al., 2020). In the present work using MCF-7, human breast cancer cells in culture we demonstrate that combined action of DDTC and B12b resulted in induction of UPRER manifested by dilation of ER cisterns, increased level of polyubiquitinated proteins, and increased expression of CHOP. Confocal microscopy revealed disorganization of mitochondrial network and ER and treatment of these cells with B12b/DDTC and accompanied by mitochondrial depolarization (~50% after 6 h of exposure to drugs). Treatments also induced changes in morphology of mitochondrial network, and within 6 h of exposure, mitochondria demonstrated large amplitude swelling, characteristic feature of mitochondrial permeability transition pore opening. Drug exposure induced mitochondrial oxidative stress and increase in superoxide anion level (monitored with MitoSOX) and increased content of mitochondrial Ca2+ (xRhod-1) which almost doubled following treatment with B12b/DDTC. Short-time exposure of MCF-7 cells to mixture of drugs in Ca2+-free incubation media (2.5 mM EGTA) resulted in generation of significantly smaller size of vacuoles as compared with control. Similarly, pre-loading of cells with intracellular Ca2+ chelator (BAPTA, 5 µM, 30 min, 37oC) or inhibition of IP3 receptor(s) with 2-APB, delayed the drug-induced vacuolization. Taken together, our data indicate that the mechanism of B12b/DDTC-induced cytotoxicity in human MCF-7 cancer cell lines involves mitochondrial oxidative stress, activation of MPT pore and Ca2+ overload. Support of Funding Information: Russian Science Foundation № 19-75-20145 Citation Format: Marina E. Solovieva. Vitamin B12 augments Ca2+ dependent cytotoxicity of diethyldithiocarbamate through excessive ER-vacuolization, oxidative stress and mitochondrial depolarization in MCF-7 cells in culture [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2032.

Study on treatment technology of industrial and mining wasteland in Shenmu City

In order to implement the basic state policy of cherishing and rationally using land and strictly protecting cultivated land, effectively break the bottleneck of strategic resource development and urban development, optimize the land use structure, raise the level of economical and intensive land use, promote the balance between urban and rural areas and the sustainable economic and social development, and realize the overall development and protection of cultivated land. In the pilot project of reclamation and utilization of historical abandoned industrial and mining lands in Shenmu City, management requirements such as total control of resource utilization, two-way regulation of supply and demand and difference are implemented to standardize the reclamation and utilization behavior of abandoned industrial and mining lands. The waste residue covered by the mining area shall be stripped and cleared, the buildings and structures in the mining area shall be dismantled, and all the waste residue and construction waste shall be transported to the designated accumulation point. Then, as needed, it will be cleared into farmland, forests, grasslands and rivers. Results: The reclamation area of the project covers 42 plots, with a total area of 2146.4 mu. The construction scale of the project is 124.8122hm2. Through the reclamation of abandoned industrial and mining land, 22.1038hm2 of new cultivated land was added in the project area, with a rate of 17.71%. The new grassland area was 32.2119hm2. After reclamation, the land utilization rate of the project increased significantly, reaching 93.38%. It promotes the balance of dynamic indexes of cultivated land in Shenmu City, maintains the dynamic balance of total cultivated land in Shaanxi Province, and improves the production and living conditions of local farmers. The project has great ecological benefit, obvious social benefit and certain economic benefit. The unification of social benefit, economic benefit and ecological benefit is realized, which accords with the goal of industrial waste land reclamation.

RNA and liquid-liquid phase separation.

Liquid-Liquid Phase Separation (LLPS) is a biological phenomenon that refers to the components of similar properties form droplets condensate in cells. These droplets play an important role in maintaining the stability of order in cells. In the studies of phase separation, weak multivalent interactions between proteins have always been the focus of attentions. With the deepening research of phase separation, more and more evidences show that RNA, especially long noncoding RNA (lncRNA), also plays an important regulatory role in the phase separation. We summarized recent researches between phase separation and RNA, and focused on the function of non-coding RNA (ncRNA) in the process of phase separation. In fact, phase separation and RNA have a two-way regulation relationship. Noncoding RNA usually recruits proteins as molecular scaffolds to drive phase separation. On the other hand, phase separation is also involved in RNA transcription, transport, metabolism and other processes.

Could the Gut Microbiota Serve as a Therapeutic Target in Ischemic Stroke?

The brain-gut axis is a relatively recent discovery of a two-way regulation system between the gut and brain, suggesting that the gut microbiota may be a promising targeted prevention and treatment strategy for patients with a high risk of acute cerebral ischemia/reperfusion injury. There are many risk factors for ischemic stroke, and many studies have shown that the gut microbiota affects the absorption and metabolism of the body, as well as the risk factors of stroke, such as blood pressure, blood glucose, blood lipids, and atherosclerosis, either directly or indirectly. Furthermore, the gut microbiota can affect the occurrence and prognosis of ischemic stroke by regulating risk factors or immune responses. Therefore, this study aimed to collect evidence of the interaction between gut microbiota and ischemic stroke, summarize the interaction mechanism between the two, and explore the gut microbiota as a new targeted prevention and treatment strategy for patients with high ischemic risk.

МЕТОДИКА МОНИТОРИНГА ДВУСТОРОННЕГО РЕГУЛИРОВАНИЯ ВЛАЖНОСТИ ПОЧВЫ ПРИ ЭКСПЛУАТАЦИИ ИНЖЕНЕРНЫХ МЕЛИОРАТИВНЫХ СИСТЕМ

The purpose of the performed research is, based on the analysis of field studies, to select a well (point) for the selection of averaged moisture in the inter-drainage space for monitoring reclamation systems, to justify the construction of drainage-humidification systems to regulate moisture in a fire-hazardous peat bog. To solve the problem, a scheme has been developed for organizing monitoring on engineering reclamation systems that provide a two-way regulation of the water regime in the root layer of the soil in the zone of unstable moisture, as well as for monitoring and ensuring fire safety of the entire peat profile. The article discusses measuring equipment for determining the dynamics of soil moisture which must be used to monitor reclamation systems. There are given the results of field studies on peat bogs of the floodplain of the Dubna River, Moscow region, namely: meteorological data and data on soil moisture. On the basis of the research carried out, a representative point of moisture sampling for monitoring of reclamation systems has been substantiated. The sampling point should be located on a typical plot with the same relief, the soil profile should be uniform with the properties and soil morphology characteristic of the entire field. Wells for sampling checks the value of the distance in ¼E (E is the distance between drains), in this case the measured value is close to the average value in relation to the entire section of the drainage-humidified system. For the soil conditions of the experimental site, the humidity in the selected well during the locking of the canal in the dry period of summer increased by 1.5 times reaching the fireproof one. It is noted that when supplying and maintaining a propped water level in a channel up to 85 cm deep for 5 or more hours, the humidity in the interdrains space rises to the value of the fire safety norm in the dry period.

Two-Way Regulation of MmpL3 Expression Identifies and Validates Inhibitors of MmpL3 Function in Mycobacterium tuberculosis.

MmpL3, an essential mycolate transporter in the inner membrane of Mycobacterium tuberculosis (Mtb), has been identified as a target of multiple, chemically diverse antitubercular drugs. However, several of these molecules seem to have secondary targets and inhibit bacterial growth by more than one mechanism. Here, we describe a cell-based assay that utilizes two-way regulation of MmpL3 expression to readily identify MmpL3-specific inhibitors. We successfully used this assay to identify a novel guanidine-based MmpL3 inhibitor from a library of 220 compounds that inhibit growth of Mtb by largely unknown mechanisms. We furthermore identified inhibitors of cytochrome bc1-aa3 oxidase as one class of off-target hits in whole-cell screens for MmpL3 inhibitors and report a novel sulfanylacetamide as a potential QcrB inhibitor.

Antibiotic-Driven Gut Microbiome Disorder Alters the Effects of Sinomenine on Morphine-Dependent Zebrafish

Morphine is one of the most severely abused drugs in the world. Previous research on morphine addiction has focused on the central nervous system (CNS). Studies have shown that a two-way regulation of the brain and gut microbiota (GM), suggesting a link between GM and CNS disease. However, the functional mechanism underlying the relationship between intestinal flora and morphine dependence is unclear. In this study, the effect of sinomenine on morphine addiction was evaluated based on the microbiota-gut-brain axis (MGBA). The results show that the GM plays an important role in morphine dependence. Morphine treatment induced zebrafish conditional position preference (CPP), and significantly changed zebrafish GM characteristics and the expression of MGBA-related genes in the zebrafish brain and intestine. Importantly, sinomenine, an alkaloid with a similar structure to morphine, can reverse these morphine-induced changes. Subsequently, morphine-dependent CPP training was performed after antibiotic administration. After antibiotic treatment, zebrafish CPP behavior, the composition and proportions of the zebrafish GM, and the expression of MGBA-related genes in zebrafish were changed. More interestingly, sinomenine was no longer effective in treating morphine dependence, indicating that antibiotic-driven intestinal flora imbalance alters the efficacy of sinomenine on morphine-dependent zebrafish. This study confirms that the MGBA is bidirectionally regulated, highlighting the key role of the GM in the formation and treatment of morphine dependence, and may provide new treatment strategies for using traditional Chinese medicine to treat drug addiction.

Different levels of rainfall and trampling change the reproductive strategy of Kobresia humilis in the Qinghai-Tibet Plateau

The sedge Kobresia humilis (C.A. Mey. ex Trautv.) Serg. is the dominant plant in the alpine meadows of China’s Qinghai-Tibet Plateau, which has experienced substantial grassland degradation due to reduced rainfall and overgrazing. In this study we sought to determine the reproductive strategy of K. humilis under three levels of rainfall and seven levels of trampling by Tibetan sheep and yaks with a two year simulation trial on the Plateau. With a reduction in rainfall and an increase in trampling intensity, there was a decrease in sexual reproduction indices, plant height and single leaf number. The highest rainfall promoted sexual reproduction, whereas average rainfall was conducive to vegetative reproduction, and the lowest rainfall inhibited reproduction. The reproductive strategy of K. humilis could be judged according to the average rainfall from July to August. Notably, after two years of low rainfall and a heavy trampling treatment, K. humilis produced more seeds with smaller size. The rainfall presented a two-way regulation function in the trampling effect on K. humilis reproductive characteristics.

Review of mechanism on astragalus membranaceus in two-ways regulation of blood pressure

Astragalus membranaceus is one of the frequently used qi tonifying herbal medicines. It can regulate blood pressure. This paper reviewed the studies on the two-way regulation of blood pressure of Astragalus membranaceus in recent years, even thought the Astragalus membranaceus has been regarded to cure hyperhension due to qi deficiency. It can lower the pressure with large dosage or in liquid-fried form. Astragalus membranaceus, Astragalus membranaceus as the sovereign drug of the formulas or Astragalus membranaceus combined with western medicine can regulate blood pressure. It was found that the effect of reducing blood pressure was mainly related to the decrease of heart rate, dilation of blood vessels, inhibition of oxidative stress, reduction of calcium ion level, diuretics, change the content of growth factor and receptor, lowering uric acid, reduction of cysteine levels, and increase insulin sensitivity.Itelevated the blood pressure, mainly related to the increase of cardiac output and vasoconstriction. Key words: Astragalus membranaceus; Blood pressure; Two-ways regulation; Review

Insight into the Effect of Small RNA srn225147 on Mutacin IV in Streptococcus mutans.

Streptococcus mutans (S. mutans) is a serious microbe causing dental caries. Mutacin IV is an effective bacteriocin produced by S. mutans to antagonize numerous non-mutans streptococcal species. However, the posttranscriptional regulation of mutacin IV remains unclear. This study aimed to analyze the effect of small RNA srn225147 on mutacin IV. The functional prediction suggested that srn225147 is involved in the production of mutacin IV, an important secondary metabolite. According to RNAhybrid and RNAPredator prediction, the mutacin IV formation-associated gene comD is a target of srn225147. We further analyzed the roles of srn225147 and comD in 20 S. mutans clinical strains with high production of mutacin IV (High-IV group) and lacking mutacin IV (None-IV group). Levels of comD expression were significantly higher in the High-IV group, whereas the Non-IV group showed relatively higher expression of srn225147, with a negative correlation observed between srn225147 and comD. Moreover, compared to the mimic negative control (NC) group, comD expression was decreased at 400-fold srn225147 overexpression but increased at approximately 1400-fold overexpression. Although the production of mutacin IV in the 1400-fold change srn225147 mimic group was larger than that in the 400-fold change mimic group, there was no significant difference in the production of mutacin IV between the srn225147 mimic group and mimic NC group. These results indicate that srn225147 has a two-way regulation effect on the expression of comD but that its regulation in the production of mutacin IV is weak.

Effects of resveratrol on proliferation and invasion of lung cancer 95D cells

Objective To study the effects of resveratrol on the proliferation and invasion capacity of human lung adenocarcinoma 95D cells. Methods Human lung adenocarcinoma 95D cells were treated with 0, 10, 20, 40, 80 μmol/L resveratrol and treated with 0 μmol/L as the control group. The proliferation level of 95D cells was measured by methyl thiazolyl tetrazolium (MTT). Cell cycle and apoptosis were detected by flow cytometry. Cell adhesion rate was determined by in vitro adhesion test. Cell invasiveness was measured by Transwell chamber. The expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitior of metalloproteinase-2 (TIMP-2) were determined by fluorescent immunocytochemistry. Results When the 95D cells were treated with resveratrol for 72 h, the cell proliferation rates in groups treated with 0, 10, 20, 40, 80 μmol/L resveratrol were 100%, (82.23±0.33)%, (62.45±0.27)%, (49.89±0.43)%, (45.11±0.35)% respectively, with a significant difference (F=87.830, P=0.002). The proliferation rates of 95D cells in the 10, 20, 40, 80 μmol/L resveratrol groups were significantly inhibited compared with the control group (P=0.017, P<0.001, P<0.001, P<0.001). When the 95D cells were treated for 48 h, the apoptosis rates of cells in each group were 0, (34.90±0.91)%, (41.33±0.13)%, (45.47±0.87)%, (59.46±0.59)% respectively, with a significant difference (F=21.032, P=0.002). The apoptosis rates of 95D cells in the 10, 20, 40, 80 μmol/L resveratrol groups were significantly increased compared with the control group (P=0.001, P<0.001, P<0.001, P<0.001). When the 95D cells were treated for 48 h, the S phase cell percentages in each group were (18.12±0.62)%, (38.33±0.62)%, (54.15±0.74)%, (44.85±0.82)%, (50.01±0.35)% respectively, with a significant difference (F=104.156, P=0.001). The S phase cell percentages in the 10, 20, 40, 80 μmol/L resveratrol groups were significantly higher compared with the control group (P=0.001, P<0.001, P<0.001, P<0.001). When the 95D cells were treated for 24 h, the cell adhesion rates in each group were 100%, (87.41±0.02)%, (84.32±0.03)%, (68.23±0.04)%, (63.01±0.02)% respectively, with a significant difference (F=13.760, P<0.001). The cell adhesion rates in the 20, 40, 80 μmol/L resveratrol groups were significantly inhibited compared with the control group (P=0.035, P<0.001, P<0.001), while the 10 μmol/L resveratrol group had no significant difference compared with the control group (P=0.058). When the 95D cells were treated for 24 h, the cell invasion rates in each group were 100%, (97.01±0.03)%, (74.89±0.07)%, (34.07±0.03)%, (14.65±0.02)% respectively, with a significant difference (F=39.382, P=0.001). The cell invasion rates in the 20, 40, 80 μmol/L groups were significantly inhibited compared with the control group (P=0.012, P<0.001, P<0.001), while the 10 μmol/L resveratrol group had no significant difference compared with the control group (P=0.881). When the 95D cells were treated for 48 h, MMP-2 protein expression was decreased in the 20 mol/L group, while TIMP-2 protein expression was increased compared with the control group. Conclusion Resveratrol can inhibit the proliferation of human lung adenocarcinoma 95D cells and has effect of anti-tumor cell invasiveness, and its mechanism may involve two-way regulation of MMP-2/TIMP-2 expression. Key words: Lung neoplasms; Cell proliferation; Cell adhesion; Neoplasm invasiveness; Resveratrol

Time-effect relationship and molecular mechanism of electroacupuncture for repair of gastric mucosal lesion

To dynamically observe the effects of electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the time-effect relationship and molecular mechanism of EA for gastric ulcer. A total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup. The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at"Zusanli"(ST 36) and"Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm next to"Zusanli"(ST 36) and"Liangmen"(ST 21); the EA was given 30 min per treatment, once a day. The rats in the normal group and model group were treated with immobilization for 30 min per day, and no EA was given. PR-PCR method was applied to test the expression of proliferating cell nuclear antigen (PCNA) and substance P (SP); Western blot method was applied to test the expression of neurotensin (NT). After 1-day treatment, the ulcer index in the model group was higher than that in the normal group (P<0.01), and the expression of PCNA, SP and NT was decreased (P<0.01, P<0.05); compared with the model group and sham acupoint group, the ulcer index was decreased in the acupoint group (both P<0.05), and the expression of PCNA and SP was up-regulated (all P<0.05) while that of NT was up-regulated (both P<0.01). After 4-day treatment, the ulcer index in the model group was reduced but still higher than that in the normal group (P<0.05), and the expression of PCNA, SP and NT was up-regulated and higher than that in the normal group (all P<0.01); the ulcer index in the acupoint group was similar to that in the normal group (P>0.05), and the expression of PCNA and SP was lower than that in the model group (P<0.01, P<0.05), and the expression of NT was not significantly different from that in the model group (P>0.05). After 7-day treatment, the differences of indexes above were not significant among the four groups (all P>0.05). EA at acupoints of stomach meridian has two-way regulation on PCNA and SP and improve the expression of NT in different pathological state of gastric ulcer, which could further improve the repair of gastric ulcer.