A Distinctive Insight into Inorganic Sonosensitizers: Design Principles and Application Domains.

Sonodynamic therapy (SDT) as a promising non-invasive anti-tumor means features the preferable penetration depth, which nevertheless, usually can't work without sonosensitizers. Sonosensitizers produce reactive oxygen species (ROS) in the presence of ultrasound to directly kill tumor cells, and concurrently activate anti-tumor immunity especially after integration with tumor microenvironment (TME)-engineered nanobiotechnologies and combined therapy. Current sonosensitizers are classified into organic and inorganic ones, and current most reviews only cover organic sonosensitizers and highlighted their anti-tumor applications. However, there have few specific reviews that focus on inorganic sonosensitizers including their design principles, microenvironment regulation, etc. In this review, inorganic sonosensitizers are first classified according to their design rationales rather than composition, and the action rationales and underlying chemistry features are highlighted. Afterward, what and how TME is regulated based on the inorganic sonosensitizers-based SDT nanoplatform with an emphasis on the TME targets-engineered nanobiotechnologies are elucidated. Additionally, the combined therapy and their applications in non-cancer diseases are also outlined. Finally, the setbacks and challenges, and proposed the potential solutions and future directions is pointed out. This review provides a comprehensive and detailed horizon on inorganic sonosensitizers, and will arouse more attentions on SDT.

The dual function of cGAS-STING signaling axis in liver diseases.

Numerous liver diseases, such as nonalcoholic fatty liver disease, hepatitis, hepatocellular carcinoma, and hepatic ischemia-reperfusion injury, have been increasingly prevalent, posing significant threats to global health. In recent decades, there has been increasing evidence linking the dysregulation of cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING)-related immune signaling to liver disorders. Both hyperactivation and deletion of STING can disrupt the immune microenvironment dysfunction, exacerbating liver disorders. Consequently, there has been a surge in research investigating medical agents or mediators targeting cGAS-STING signaling. Interestingly, therapeutic manipulation of the cGAS-STING pathway has yielded inconsistent and even contradictory effects on different liver diseases due to the distinct physiological characteristics of intrahepatic cells that express and respond to STING. In this review, we comprehensively summarize recent advancements in understanding the dual roles of the STING pathway, highlighting that the benefits of targeting STING signaling depend on the specific types of target cells and stages of liver injury. Additionally, we offer a novel perspective on the suitability of STING agonists and antagonists for clinical assessment. In conclusion, STING signaling remains a highly promising therapeutic target, and the development of STING pathway modulators holds great potential for the treatment of liver diseases.

Transcription Factor EGR1 Facilitates Neovascularization in Mice with Retinopathy of Prematurity by Regulating the miR-182-5p/EFNA5 Axis.

Neovascularization is the hallmark of retinopathy of prematurity (ROP). Early growth response 1 (EGR1) has been reported as an angiogenic factor. This study was conducted to probe the regulatory mechanism of EGR1 in neovascularization in ROP model mice. The ROP mouse model was established, followed by determination of EGR1 expression and assessment of neovascularization [vascular endothelial growth factor-A (VEGF-A) and pigment epithelium-derived factor (PEDF)]. Retinal vascular endothelial cells were cultured and treated with hypoxia, followed by the tube formation assay. The state of oxygen induction was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay to determine hypoxia-inducible factor 1-alpha (HIF-1A). The levels of microRNA (miRNA)-182-5p and ephrin-A5 (EFNA5) in tissues and cells were determined by RT-qPCR. Chromatin immunoprecipitation and dual-luciferase assay were used to validate gene interaction. EGR1 and EFNA5 were upregulated in the retina of ROP mice while miR-182-5p was downregulated. EGR1 knockdown decreased VEGF-A and HIF-1A expression and increased PEDF expression in the retina of ROP mice. In vitro, EGR1 knockdown also reduced neovascularization. EGR1 binding to the miR-182-5p promoter inhibited miR-182-5p transcription and further promoted EFNA5 transcription. miR-182-5p downregulation or EFNA5 overexpression averted the inhibition of neovascularization caused by EGR1 downregulation. Overall, EGR1 bound to the miR-182-5p promoter to inhibit miR-182-5p transcription and further promoted EFNA5 transcription, thus promoting retinal neovascularization in ROP mice.

Unconventional photon blockade in a non-Hermitian indirectly coupled resonator system.

Photon blockade provides an effective way to realize the single-photon source, which attracts intensive attention in the fields of quantum optics and quantum information. Here in this study, we investigate photon blockade in a non-Hermitian indirectly coupled resonator system, which consists of a dissipative cavity and a Kerr nonlinear resonator coupled to two nano-scatters. We find that by tuning the coupling phase θ between the two resonators, the quantum interference could be induced on one side near the exceptional points (EPs), resulting in the unconventional photon blockade effect. Furthermore, it is noticed that the large Kerr nonlinearity is not always beneficial for unconventional photon blockades. There is an optimal threshold for the intensity of the Kerr nonlinearity and the phase angle θ for the appearance of the unconventional photon blockade effect. We believe the current study has substantial consequences for investigating the physical characteristics close to EPs and presents a novel method for developing integrated on-chip single-photon sources.

A Systematic Review and Meta-Analysis of the Association between Residual Shunts after Patent Foramen Ovale Closure and Long-Term Cerebrovascular Events.

BACKGROUND: The association between a patent foramen ovale (PFO) and cryptogenic stroke (CS) is well established, and the benefits of PFO closure are clearly recognized. This study aimed to investigate the presence of a residual shunt in patients who have experienced cryptogenic cerebrovascular events following a PFO closure. METHODS: Two researchers systematically searched the PubMed and Embase online database for pertinent clinical studies published between January 2000 and July 2021 concerning the recurrence of cerebrovascular events after PFO closures. RESULTS: Upon screening an initial list of 2,342 articles, six studies were identified, involving 2,083 patients. Overall, the analysis indicated a marked difference in the recurrence of cerebrovascular events in 8.89% of residual shunt (RS) cases compared to only 2.90% of non-RS cases. The summary odds ratio was 3.484 (95% confidence interval, 2.169-5.596), which suggested that RS may be a risk factor for recurrent cerebrovascular events in patients that experienced PFO-related cerebrovascular events within 6 months after PFO closure surgery. CONCLUSIONS: The presence of RS significantly increases the risk of recurrent cerebrovascular events in patients with clinical PFO closure.

LncRNA H19-EZH2 interaction promotes liver fibrosis via reprogramming H3K27me3 profiles.

Liver fibrosis is a wound-healing process characterized by excess formation of extracellular matrix (ECM) from activated hepatic stellate cells (HSCs). Previous studies show that both EZH2, an epigenetic regulator that catalyzes lysine 27 trimethylation on histone 3 (H3K27me3), and long non-coding RNA H19 are highly correlated with fibrogenesis. In the current study, we investigated the underlying mechanisms. Various models of liver fibrosis including Mdr2-/-, bile duct ligation (BDL) and CCl4 mice were adapted. We found that EZH2 was markedly upregulated and correlated with H19 and fibrotic markers expression in these models. Administration of EZH2 inhibitor 3-DZNeP caused significant protective effects in these models. Furthermore, treatment with 3-DZNeP or GSK126 significantly inhibited primary HSC activation and proliferation in TGF-ß-treated HSCs and H19-overexpreesing LX2 cells in vivo. Using RNA-pull down assay combined with RNA immunoprecipitation, we demonstrated that H19 could directly bind to EZH2. Integrated analysis of RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) further revealed that H19 regulated the reprogramming of EZH2-mediated H3K27me3 profiles, which epigenetically promoted several pathways favoring HSCs activation and proliferation, including epithelial-mesenchymal transition and Wnt/ß-catenin signaling. In conclusion, highly expressed H19 in chronic liver diseases promotes fibrogenesis by reprogramming EZH2-mediated epigenetic regulation of HSCs activation. Targeting the H19-EZH2 interaction may serve as a novel therapeutic approach for liver fibrosis.

BRD4 inhibition by JQ1 protects against LPS-induced cardiac dysfunction by inhibiting activation of NLRP3 inflammasomes.

BACKGROUND: JQ1, a BRD4 inhibitor, first identified its therapeutic role in cancer, has gradually demonstrated a protective effect on the heart in recent years; however, it is unclear whether JQ1 also plays a role in LPS-induced cardiac dysfunction. METHODS AND RESULTS: A total of forty eight mice were randomly divided into control, LPS(7.5 mg/kg), and LPS + JQ1 (50 mg/kg). JQ1 was preprotected for 1 h, and LPS was stimulated for 12 h, mouse survival and cardiac function were observed, and histopathological, serum myocardial injury markers, and inflammatory indicators, and oxidative stress levels in heart tissue were examined. The experiment found that the cardiac BRD4 levels were upregulated and the heart severe damage in the LPS group compared with the control group. While compared with the LPS group, JQ1 preprotected increased survival rate and cardiac function, reducated cardiomypathological injury and CD45 infiltration, and reduced the release of LDH, CK-MB, IL-1, IL-18, reduced MDA generation, and increased SOD viability. In addition, JQ1 preprotected also upregulated SIRT1, and inhibited the expression of NLRP3, caspase-1p20, and GSDMD. Meanwhile, similar results were obtained in LPS-treated H9C2 cells, and further intervention with the SIRT1 inhibitor EX527 partially blocked the JQ1-mediated down regulation of NLRP3, caspase-1p20, and GSDMD. CONCLUSIONS: We propose that JQ1 may improve LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes, which may be a promising strategy for treating sepsis cardiomyopathy.

Supramolecular Chemotherapy: Host-Guest Complexes of Heptaplatin-Cucurbit[7]uril toward Colorectal Normal and Tumor Cells.

Supramolecular chemotherapy is a strategy that is currently used to improve the therapeutic efficacy of traditional chemotherapy while mitigating side effects. Heptaplatin, a platinum chemotherapeutic antitumor drug in colorectal tumors, is traditionally used in the clinic. However, its side effects and low efficiency in killing tumors remain unresolved. Herein, a facile supramolecular chemotherapy platform on account of the host-guest chemistry between cucurbit[7]uril and the commercially available heptaplatin was studied. At pH 7.4, heptaplatin showed a strong binding to the cucurbit[7]uril nanocarrier by 1H NMR, whose Ka was (1.38 ± 0.06) × 106 M-1 by isothermal titration calorimetry (ITC). At pH 6.0 in a tumor microenvironment, overexpressed spermine can exchange competitively heptaplatin from heptaplatin-CB[7]. This supramolecular complex achieved higher antitumor activity on colorectal tumor cells and lower cytotoxicity than the drug alone on colorectal normal cells. Furthermore, the antitumor mechanisms of supramolecular complex were investigated by apoptosis, cell cycle, and spermine synthase. It was found that heptaplatin-CB[7] consumed more colorectal tumorous intracellular spermine by the spermine synthase assay (413.85 ± 0.004 pg/mL); hepataplatin-CB[7] caused early apoptosis (87.73%) of colorectal tumor cells; heptaplatin-CB[7] induced an inhibitory response in the G1 phase of the tumor cell cycle. These findings demonstrated that heptaplatin-CB[7] had higher antitumor activity toward human colorectal tumor cells but lower cytotoxicity toward human colorectal normal cells. It is expected to promote the supramolecular chemotherapy and translational development of the nanocomplex into the clinical field.

Sex differences and psychological stress: responses to the COVID-19 pandemic in China.

BACKGROUND: About 83,000 COVID-19 patients were confirmed in China up to May 2020. Amid the well-documented threats to physical health, the effects of this public health crisis - and the varied efforts to contain its spread - have altered individuals' "normal" daily functioning. These impacts on social, psychological, and emotional well-being remain relatively unexplored - in particular, the ways in which Chinese men and women experience and respond to potential behavioral stressors. Our study investigated sex differences in psychological stress, emotional reactions, and behavioral responses to COVID-19 and related threats among Chinese residents. METHODS: In late February (2020), an anonymous online questionnaire was disseminated via WeChat, a popular social media platform in China. The cross-sectional study utilized a non-probabilistic "snowball" or convenience sampling of residents from various provinces and regions of China. Basic demographic characteristics (e.g., age and gender) - along with residential living arrangements and conditions - were measured along with psychological stress and emotional responses to the COVID-19 pandemic. RESULTS: Three thousand eighty-eight questionnaires were returned: 1749 females (56.6%) and 1339 males (43.4%). The mean stress level,as measured by a visual analog scale, was 3.4 (SD = 2.4) - but differed significantly by sex. Besides sex, factors positively associated with stress included: age (< 45 years), employment (unsteady income, unemployed), risk of infection (exposureto COVID-19, completed medical observation), difficulties encountered (diseases, work/study, financial, mental), and related behaviors (higher desire for COVID-19 knowledge, more time concerning on the COVID-19 outbreak). "Protective" factors included frequent contact with colleagues, calmness of mood comparing with the pre-pandemic, and psychological resilience. Males and females also differed significantly in adapting to current living/working, conditions, responding to run a fever, and needing psychological support services. CONCLUSIONS: The self-reported stress of Chinese residents related to the COVID-19 pandemic was significantly related to sex, age, employment, resilience and coping styles. Future responses to such public health threats may wish to provide sex- and/or age-appropriate supports for psychological health and emotional well-being to those at greatest risk of experiencing stress.

Effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia: a multicenter study in Hubei Province, China. / çª’æ¯æ–°ç”Ÿå„¿ç³–ä»£è°¢ç´Šä¹±å¯¹è¿‘æœŸé¢„åŽçš„å½±å“ï¼šä¸€é¡¹æ¹–åŒ—çœå¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, P<0.05) or with severe asphyxia (19.8% vs 8.1%, P<0.05) or hypothermia therapy (4.8% vs 1.5%, P<0.05), as well as a significantly higher incidence rate of disorder of glucose metabolism (18.8% vs 12.5%, P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly higher incidence rate of disorder of glucose metabolism at 1, 2, and 6 hours after birth (P<0.05). The multivariate logistic regression analysis showed that recurrent hyperglycemia (adjusted odds ratio=2.380, 95% confidence interval: 1.275-4.442, P<0.05) was an independent risk factor for poor prognosis in neonates with asphyxia. CONCLUSIONS: Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.

Novel nonsense mutation p. Gln264Ter in the ANK1 confirms causative role for hereditary spherocytosis: a case report.

BACKGROUND: Hereditary spherocytosis (HS) is the most common haemolytic anaemia caused by congenital membrane defects of red blood cells. The name derives from the presence of spherical red blood cells in the peripheral blood. Clinical manifestations of HS are anaemia, haemolytic jaundice, and large spleen, and infection can worsen the condition, often with cholelithiasis. HS is mainly caused by abnormal functions of the products of six genes. Splenectomy is the main treatment for HS. CASE PRESENTATION: Half a day after birth, the proband exhibited HS-related symptoms, with progressive aggravation. Routine examination in the outpatient department showed an increase in white blood cells and a decrease in red blood cells. His mother had HS and a partial splenectomy. We suspected that the infant might also have HS. Genomic DNA samples were extracted from the three members of the HS trio pedigree, and genomic whole-exome sequencing (WES) was performed. The three DNA samples were amplified by polymerase chain reaction (PCR), followed by Sanger sequencing to identify mutation sites. A novel nonsense heterozygous mutation, c.790C > T (p. Gln264Ter), in the ANK1 gene, which causes premature termination of translation, was found in this Chinese family with autosomal dominant HS. CONCLUSIONS: This de novo nonsense mutation can cause the onset of HS in early childhood, with severe symptoms. Expanding the ANK1 genotype mutation spectrum will lay a foundation for the further application of mutation screening in genetic counselling.

Gender differences of depression and anxiety among social media users during the COVID-19 outbreak in China:a cross-sectional study.

BACKGROUND: Studies have shown that the outbreak of infectious diseases would result in mental health problems. Females are in greater risk for psychological problems than males. The present study investigated gender differences of depression and anxiety and explored associated factors during the COVID-19 epidemic among Chinese social media users. METHODS: We recruited 3088 participants through social media cross China. Participants completed sociodemographic and the COVID-19 epidemic related questions, the 2-item Patient Health Questionnaire (PHQ-2), and the 2-item Generalized Anxiety Disorder Scale (GAD-2), the Chinese version of the 10-item Connor-Davidson Resilience Scale. We applied Chi-square test and ANOVA for data description and linear regression analysis for exploring factors associated with depression and anxiety. RESULTS: Of 3063 participants eligible for analysis, the total prevalence of depression and anxiety was 14.14 and 13.25%. Females were experiencing more severe stress and anxiety symptoms, while males showed better resilience to stress. The severity of depression symptoms would decrease with the increase of age resilience, and it would increase if being unemployed, feeling less adapted, being more stressed. The severity of anxiety symptoms would decrease with higher education and better resilience, and it would increase if being female, spending over 60 min on COVID-19 related information, less adapted, and being more stressed. CONCLUSION: The findings show the increased prevalence of depression and anxiety in Chinese population during the COVID-19 epidemic, and females are experiencing more severe anxiety symptoms than males. As social media is the current main resource of information related to COVID-19, interventions should be implemented to help users to limit the time they spend on social media and to get key information related to the epidemic from authoritative and authentic resource to avoid infodemic and prevent mental health problems.

[Association analysis of phenotypic traits of alkaloid content in Sophora alopecuroides with SSR molecular markers].

To further study and fully exploit the medicinal plant Sophora alopecuroides, the molecular markers related with the phenotypic traits of alkaloid content in S. alopecuroides should be detected. In this study, SSR molecular markers were used to analyze the genetic diversity and genetic structure of 23 S. alopecuroides populations, in combination with the association analysis between molecular markers and the alkaloid contents. The results showed that P, H, I, G_(st) and N_m values were 40.10%, 0.335 3, 0.504 5, 0.433 7 and 0.625 9 respectively, in 23 S. alopecuroides populations. This indicated that there was less gene exchange and higher genetic differentiation among different S. alopecuroides populations. The results of SSR unweighted pair-group method with arithmetic means(UPGMA) cluster showed that the S. alopecuroides populations relationship from Xinjiang was far from the populations of other regions, but the populations of S. alopecuroides from Gansu, Inner Mongolia and Qinghai were closely relevant to those from Ningxia. The 23 populations were further divided into 2 genetic subpopulations by the population structure analysis. Through association analysis, a total of 26 loci in 13 SSR markers were found to be significantly associated(P<0.005)with the content of MA, OMA, SC and OSC, and the rate of explanation on the phenotype variance of related markers ranged from 36.45% to 77.93%. Among the locus, 1 each were related with MA and OSC content at interpretation rate reached as high as 50% with high threshold(P<0.000 1). These results could provide support for the discovery of important genes in the alkaloid biosynthetic and metabolic pathway of S. alopecuroides.

A Multicentered Randomized Study on Early versus Rescue Calsurf Administration for the Treatment of Respiratory Distress Syndrome in Preterm Infants.

OBJECTIVE: Surfactant and noninvasive ventilation are two major strategies for the treatment of neonates with respiratory distress syndrome (RDS). However, the optimal time for surfactant administering is yet controversial. This study compared the early and rescue Calsurf administration in preterm infants with RDS. STUDY DESIGN: Preterm infants born between 260/7 and 326/7 weeks of gestation and needed nasal continuous positive airway pressure (nCPAP) immediately after birth were randomly assigned to the early or rescue Calsurf treatment group. In the early treatment group, neonates were intubated, administered surfactant with bag-mask ventilation, and extubated to nCPAP (INSURE [intubation-surfactant-extubation]). In the rescue treatment group, InSurE was given until the clinical manifestation and chest X-ray displayed RDS. The primary outcome was to compare the reintubation rate within 72 hour age between the two groups. RESULTS: Among 305 neonates randomized to the early (n = 154) and rescue (n = 151) groups, the reintubation rate within 72 hours of age in these two groups did not differ significantly (p > 0.05). The incidence of oxygen dependence until 36 weeks' corrected age was similar in both groups. CONCLUSION: No differences were observed between early and rescue Calsurf treatment groups with respect to the reintubation rate within 72 hours of age and the incidence of bronchopulmonary dysplasia.

The effect of vitamin D auxiliary rehabilitation therapy in children with cerebral palsy and language dysfunction.

BACKGROUND: The aim of the present study was to observe the clinical efficacy of vitamin D auxiliary rehabilitation therapy in children with cerebral palsy and language dysfunction. METHODS: Eighty-two cases of children with cerebral palsy and language dysfunction in our hospital from March 2011 to June 2014 were selected for this study. They were divided into two groups: the rehabilitation treatment group (simple group, N.=39) and the vitamin D auxiliary rehabilitation therapy group (combination group, N.=43). After three months of treatment, language development, Gesell Child Development Scale, Bayley Infant Development Scale score and vitamin D and calcium levels were compared. RESULTS: The language development, Gesell Child Development Scale, Bayley Infant Development Scale score and vitamin D and calcium levels for two of the groups, after treatment, are improved compared to before treatment. The difference was statistically significant (P<0.05). The total efficiency of the language development in the combination group was obviously higher than the simple group. The difference was significant (95.3% vs. 74.4%, χ2=2.486, P=0.032). The Gesell Child Development Scale improved in the combination group compared to the simple group. The difference was statistically significant (70.4±11.3 vs. 53.3±10.5, t=3.127, P=0.026). The proportion of normal children was significantly higher than the rehabilitation treatment group, and the difference was statistically significant (30.2% vs. 20.5%, χ2=3.016, P=0.029). In the combination group, the vitamin D and calcium levels were statistically increased compared to the rehabilitation treatment group. It had statistical differences between the two groups (P<0.05). CONCLUSIONS: Vitamin D auxiliary rehabilitation therapy could improve the language function and the language development status in children with cerebral palsy and language dysfunction.

Plasmonic Metasurfaces Based on Nanopin-Cavity Resonator for Quantitative Colorimetric Ricin Sensing.

In view of the toxic potential of a bioweapon threat, rapid visual recognition and sensing of ricin has been of considerable interest while remaining a challenging task up to date. In this study, a gold nanopin-based colorimetric sensor is developed realizing a multicolor variation for ricin qualitative recognition and analysis. It is revealed that such plasmonic metasurfaces based on nanopin-cavity resonator exhibit reflective color appearance, due to the excitation of standing-wave resonances of narrow bandwidth in visible region. This clear color variation is a consequence of the reflective color mixing defined by different resonant wavelengths. In addition, the colored metasurfaces appear sharp color difference in a narrow refractive index range, which makes them especially well-suited for sensing applications. Therefore, this antibody-functionalized nanopin-cavity biosensor features high sensitivity and fast response, allowing for visual quantitative ricin detection within the range of 10-120 ng mL-1 (0.15 × 10-9 -1.8 × 10-9 m), a limit of detection of 10 ng mL-1 , and the typical measurement time of less than 10 min. The on-chip integration of such nanopin metasurfaces to portable colorimetric microfluidic device may be envisaged for the quantitative studies of a variety of biochemical molecules.

Concentration of entangled nitrogen-vacancy centers in decoherence free subspace.

Exploiting the input-output process of low-Q cavities confining nitrogen-vacancy centers, we present an efficient entanglement concentration protocol on electron spin state in decoherence free subspace. Less entangled state can be concentrated to maximally entangled state with the assistance of single photon detection. With its robustness and scalability, the present protocol is immune to dephasing and can be further applied to quantum repeaters and distributed quantum computation.

[Hesperetin attenuates angiotensin II-induced collagen expression in cardiac fibroblasts in vitro].

OBJECTIVE: To explore the effect of hesperetin (HES) on collagen expression in cardiac fibroblasts in vitro induced by angiotensin II (AngII). METHODS: Cell growth was determined by trypan blue staining, reactive oxygen species (ROS) generation by microplate reader, the expressions of collagen I,III and matrix metalloproteinase 1 (MMP-1) by real-time polymerase chain reaction (PCR) and cell proliferation by cell counting kit-8. RESULTS: HES and AngII+HES had no effect on cellular activity. AngII significantly increased ROS generation (1.70 ± 0.12 vs 1, P < 0.01), gene expression of collagen I,III both increased (1.31 ± 0.08 vs 1, 1.40 ± 0.09 vs 1, both P < 0.01) while MMP-1 decreased (0.68 ± 0.03 vs 1, P < 0.01). Ang II also induced the proliferation of fibroblasts (1.91 ± 0.18 vs 1, P < 0.01). While HES (25, 50, 100 µmol/L) or NAC (1 mmol/L) reversed these effects during co-treating with AngII, ROS decreased versus the Ang II group(1.37 ± 0.05, 1.16 ± 0.08, 1.07 ± 0.07, 1.12 ± 0.07 vs 1.70 ± 0.12, all P < 0.01) , gene expression of collagenI,III also decreased (1.22 ± 0.08 and 1.27 ± 0.07, 1.14 ± 0.07 and 1.00 ± 0.06, 1.02 ± 0.06 and 0.99 ± 0.05, 1.08 ± 0.07 and 1.09 ± 0.06 vs 1.31 ± 0.08 and 1.40 ± 0.09, all P < 0.01), MMP-1 increased (0.76 ± 0.05, 0.88 ± 0.07, 1.01 ± 0.08, 0.96 ± 0.07 vs 0.68 ± 0.03, P < 0.01) versus the Ang II group. Cell proliferation was also inhibited (1.42 ± 0.07, 1.38 ± 0.03, 1.07 ± 0.15, 1.16 ± 0.11 vs 1.91 ± 0.18, all P < 0.01). NAC had the same effect with HES. CONCLUSION: HES inhibits the synthesis of collagen and the Ang II-induced proliferation of fibroblast through suppressing the ROS generation.

Physiochemically and Genetically Engineered Bacteria: Instructive Design Principles and Diverse Applications.

With the comprehensive understanding of microorganisms and the rapid advances of physiochemical engineering and bioengineering technologies, scientists are advancing rationally-engineered bacteria as emerging drugs for treating various diseases in clinical disease management. Engineered bacteria specifically refer to advanced physiochemical or genetic technologies in combination with cutting edge nanotechnology or physical technologies, which have been validated to play significant roles in lysing tumors, regulating immunity, influencing the metabolic pathways, etc. However, there has no specific reviews that concurrently cover physiochemically- and genetically-engineered bacteria and their derivatives yet, let alone their distinctive design principles and various functions and applications. Herein, the applications of physiochemically and genetically-engineered bacteria, and classify and discuss significant breakthroughs with an emphasis on their specific design principles and engineering methods objective to different specific uses and diseases beyond cancer is described. The combined strategies for developing in vivo biotherapeutic agents based on these physiochemically- and genetically-engineered bacteria or bacterial derivatives, and elucidated how they repress cancer and other diseases is also underlined. Additionally, the challenges faced by clinical translation and the future development directions are discussed. This review is expected to provide an overall impression on physiochemically- and genetically-engineered bacteria and enlighten more researchers.

Plant-derived exosome-like nanovesicles: A novel nanotool for disease therapy.

Exosomes are extracellular vesicles comprising bilayer phospholipid membranes and are secreted by eukaryotic cells. They are released via cellular exocytosis, contain DNA, RNA, proteins, and other substances, and participate in various cellular communications between tissues and organs. Since the discovery of exosomes in 1983, animal-derived exosomes have become a research focus for small-molecule drug delivery in biology, medicine, and other fields owing to their good biocompatibility and homing effects. Recent studies have found that plant-derived exosome-like nanovesicles (PELNVs) exhibit certain biological effects, such as anti-inflammatory and anti-tumor abilities, and have minimal toxic side effects. Because they are rich in active lipid molecules with certain pharmacological effects, PELNVs could be novel carriers for drug delivery. In this review, the biological formation and effects, isolation, and extraction of PELNVs, as well as characteristics of transporting drugs as carriers are summarized to provide new ideas and methods for future research on plant-derived exosome-like nanovesicles.