Antibiotics played an important role in controlling the development of enteric infection. However, the emergence of antibiotic resistance and gut dysbiosis led to a growing interest in the use of ...natural antimicrobial agents as alternatives for therapy and disinfection. Chitosan is a nontoxic natural antimicrobial polymer and is approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration). Chitosan and chitosan derivatives can kill microbes by neutralizing negative charges on the microbial surface. Besides, chemical modifications give chitosan derivatives better water solubility and antimicrobial property. This review gives an overview of the preparation of chitosan, its derivatives, and the conjugates with other polymers and nanoparticles with better antimicrobial properties, explains the direct and indirect mechanisms of action of chitosan, and summarizes current treatment for enteric infections as well as the role of chitosan and chitosan derivatives in the antimicrobial agents in enteric infections. Finally, we suggested future directions for further research to improve the treatment of enteric infections and to develop more useful chitosan derivatives and conjugates.
Here we present, to date, the highest‐resolved (~5 years) and most precisely dated Holocene monsoon climate reconstruction for the western Chinese Loess Plateau based on five replicated stalagmite ...δ18O records from Wuya Cave, eastern Gansu, China. Our record suggests the wettest period occurred between 10,500 and 6,600 a BP in this region. After this period, the amplitude of Asian summer monsoon decadal‐scale variability progressively increased likely in response to increasing ENSO frequency since the middle Holocene. Our study reveals similar asymmetric centennial‐scale double‐plunging structures of the 8.2, 5.5, and 2.8 ka events in the western Chinese Loess Plateau, suggesting a possible role of solar activity whose impact was amplified around 8.2 ka BP by the meltwater flood. In contrast, the 4.2 ka event exhibit gradually declining monsoon rainfall with centennial‐ to decadal‐scale fluctuations.
Key Points
A 5 year‐resolved Holocene Asian summer monsoon record was reconstructed for the western Loess Plateau based on speleothems
The wettest period occurred between 10,500 and 6,600 a BP, after that, the amplitude of decadal‐scale monsoon variability increased
Similar structures were observed during the 8.2, 5.5, and 2.8 ka weak monsoon events, which are different from the 4.2 ka event
RATIONALE:Generation of induced cardiac myocytes (iCMs) directly from fibroblasts offers great opportunities for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation ...is the low conversion rate of fibroblasts to fully reprogrammed iCMs, which could in part be attributed to unbalanced expression of reprogramming factors Gata4 (G), Mef2c (M), and Tbx5 (T) using the current gene delivery approach.
OBJECTIVE:We aimed to establish a system to express distinct ratios of G, M, T proteins in fibroblasts and determine the effect of G, M, T stoichiometry on iCM reprogramming.
METHODS AND RESULTS:We took advantage of the inherent feature of the polycistronic system and generated all possible combinations of G, M, T with identical 2A sequences in a single transgene. We demonstrated that each splicing order of G, M, T gave rise to distinct G, M, T protein expression levels. Combinations that resulted in higher protein level of Mef2c with lower levels of Gata4 and Tbx5 significantly enhanced reprogramming efficiency compared with separate G, M, T transduction. Importantly, after further optimization, the MGT vector resulted in more than 10-fold increase in the number of mature beating iCM loci. Molecular characterization revealed that more optimal G, M, T stoichiometry correlated with higher expression of mature cardiac myocyte markers.
CONCLUSIONS:Our results demonstrate that stoichiometry of G, M, T protein expression influences the efficiency and quality of iCM reprogramming. The established optimal G, M, T expression condition will provide a valuable platform for future iCM studies.
Functional cardiac tissue engineering holds promise as a candidate therapy for myocardial infarction and heart failure. Generation of “strong-contracting and fast-conducting” cardiac tissue patches ...capable of electromechanical coupling with host myocardium could allow efficient improvement of heart function without increased arrhythmogenic risks. Towards that goal, we engineered highly functional 1 cm × 1 cm cardiac tissue patches made of neonatal rat ventricular cells which after 2 weeks of culture exhibited force of contraction of 18.0 ± 1.4 mN, conduction velocity (CV) of 32.3 ± 1.8 cm/s, and sustained chronic activation when paced at rates as high as 8.7 ± 0.8 Hz. Patches transduced with genetically-encoded calcium indicator (GCaMP6) were implanted onto adult rat ventricles and after 4–6 weeks assessed for action potential conduction and electrical integration by two-camera optical mapping of GCaMP6-reported Ca2+ transients in the patch and RH237-reported action potentials in the recipient heart. Of the 13 implanted patches, 11 (85%) engrafted, maintained structural integrity, and conducted action potentials with average CVs and Ca2+ transient durations comparable to those before implantation. Despite preserved graft electrical properties, no anterograde or retrograde conduction could be induced between the patch and host cardiomyocytes, indicating lack of electrical integration. Electrical properties of the underlying myocardium were not changed by the engrafted patch. From immunostaining analyses, implanted patches were highly vascularized and expressed abundant electromechanical junctions, but remained separated from the epicardium by a non-myocyte layer. In summary, our studies demonstrate generation of highly functional cardiac tissue patches that can robustly engraft on the epicardial surface, vascularize, and maintain electrical function, but do not couple with host tissue. The lack of graft-host electrical integration is therefore a critical obstacle to development of efficient tissue engineering therapies for heart repair.
Ethnopharmacological relevance:
Hypericum sampsonii Hance, also known as Yuanbao Cao in Chinese, is a traditional medicinal herb from the Guttiferae family and has been widely used in China to treat ...various conditions, including dysentery, enteritis, mastitis, scrofula, and contusion.
Aim of the review:
This review aims to provide a comprehensive overview of the botany, traditional uses, phytochemistry, biological activity and safety of
H. sampsonii
and to highlight its potential for medical application and drug development.
Materials and methods:
We searched several databases, i.e., Web of Science, SciFinder, PubMed, CBM, CNKI, Google Scholar, etc., for relevant information on
H. sampsonii
. Additionally, we also consulted some books on Chinese medicine.
Results:
To date, 227 secondary metabolites have been isolated from
H. sampsonii
, including polycyclic polyprenylated acylphloroglucinols (PPAPs), benzophenones, xanthones, flavonoids, naphthodianthrones, anthraquinones and aromatic compounds. These metabolites exhibit various biological activities such as anti-inflammatory, anti-tumor, anti-depressant, anti-oxidant, anti-viral and anti-bacterial effects. PPAPs are considered the main active metabolites with rich biological activities. Despite being known as rich source of PPAPs, the full extent of
H. sampsonii
biological activities, including their potential as PDE4 inhibitors, remained unclear. Since, previous studies have mainly been based on structural identification of metabolites in
H. sampsonii
, and efficacy evaluations of these metabolites based on clinical applications of
H. sampsonii
lack sufficient data. However, current evidence suggest that PPAPs are the most likely material basis for efficacy. From the limited information available so far, there is no evidence of potential safety issues and the safety data are limited.
Conclusion:
Collectively, this review provides a comprehensive overview of the botany, traditional uses, phytochemistry, pharmacology, and safety of
H. sampsonii
, a valuable medicinal plant in China with various pharmacological activities. Based on pharmacological studies,
H. sampsonii
shows potential for treating gastrointestinal and gynecological disorders as well as traumatic injuries, which aligns with traditional medicinal use due to the presence of PPAPs, benzophenones, xanthones, and flavonoids. Therefore, further studies are needed to evaluate the pharmacological effects and elucidate the pharmacological mechanisms. In addition, pharmacological mechanisms and safety evaluation of PPAPs on animal models need to be clarified. Yet, further comprehensive studies are required to elucidate the phytochemical constituents, pharmacological mechanisms, structure-activity relationships, safety evaluation, and quality standards of this plant. Takentogether, this review highlights the potential of
H. sampsonii
for medical application and drug development.
Maintaining undifferentiated mouse embryonic stem cell (mESC) culture has been a major challenge as mESCs cultured in Leukemia Inhibitory Factor (LIF) conditions exhibit spontaneous differentiation, ...fluctuating expression of pluripotency genes, and genes of specialized cells. Here we show that, in sharp contrast to the mESCs seeded on the conventional rigid substrates, the mESCs cultured on the soft substrates that match the intrinsic stiffness of the mESCs and in the absence of exogenous LIF for 5 days, surprisingly still generated homogeneous undifferentiated colonies, maintained high levels of Oct3/4, Nanog, and Alkaline Phosphatase (AP) activities, and formed embryoid bodies and teratomas efficiently. A different line of mESCs, cultured on the soft substrates without exogenous LIF, maintained the capacity of generating homogeneous undifferentiated colonies with relatively high levels of Oct3/4 and AP activities, up to at least 15 passages, suggesting that this soft substrate approach applies to long term culture of different mESC lines. mESC colonies on these soft substrates without LIF generated low cell-matrix tractions and low stiffness. Both tractions and stiffness of the colonies increased with substrate stiffness, accompanied by downregulation of Oct3/4 expression. Our findings demonstrate that mESC self-renewal and pluripotency can be maintained homogeneously on soft substrates via the biophysical mechanism of facilitating generation of low cell-matrix tractions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery was ...developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle–doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody–antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity.
IntroductionUlcerative colitis (UC) is a global chronic inflammatory bowel disease, and the poor efficacy of currently available pharmacological regimens makes the management of UC a great challenge. ...Moxibustion has shown great potential in the management of UC. However, its effectiveness and safety are still controversial. The purpose of this study is to synthesise the latest evidence regarding the clinical efficacy and safety of moxibustion for UC.Methods and analysisThe Cochrane Library, PubMed, EMBASE, CNKI, Wanfang, VIP and SinoMed databases will be searched from inception to July 2023, to identify all randomised controlled trials with moxibustion for UC. The primary outcome will be clinical efficacy, as measured by validated scales. The serum inflammatory factor, colonoscopy results, quality of life, recurrence rate and adverse events will be the secondary outcomes. The Cochrane Risk of Bias 2.0 tool will be used to assess the methodological quality of each included trial. All data extraction will be carried out independently by two investigators. RevMan V.5.4 software will be used for data analysis and Cochran’s Q statistic and I2 test will be used to assess heterogeneity between studies. In addition, we will perform subgroup analyses, sensitivity analyses and publication bias if the available data are sufficient. The strength of evidence will be graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.Ethics and disseminationEthics approval is not required for this review. Our findings will be published in a peer-reviewed journal.PROSPERO registration numberCRD42023425481.
In recent years, more and more record-breaking extreme weather/climate events have been reported from the Asian monsoon region, which have caused tremendous loss of property and lives. In this paper, ...we analyzed the Asian summer monsoon (ASM) variability during the Holocene and evaluated future climate extremes in monsoonal China from a paleoclimatic view. We found a significant regime transition to more chaotic fluctuations, with enhanced decadal variability of the ASM since 6.6 ka BP. We suggested the gradual intensification of ENSO was responsible for enhancing the ASM variability since the late mid-Holocene. If the observed relationship of monsoon mean intensity, ENSO and decadal variability of the ASM in the past 11.2 ka continue to exist, enhanced decadal variability of ASM in the future warming world will be expected. As a result, the intensification of daily precipitation extremes, superimposed on enhanced decadal variability of ASM, might make the record-breaking extremes more frequent in the future, increasing the risk of climate-related disasters in China.
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high incidence, high malignancy, and low survival rate. Cuproptosis is a novel form of cell death mediated by ...lipoylated TCA cycle proteins-mediated novel cell death pathway and is highly associated with mitochondrial metabolism. However, the relationship between the expression level of cuproptosis-related genes (CRGs) and the prognosis of HCC is still unclear.
Combining the HCC transcriptomic data from The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed cuproptosis-related genes (DECRGs) and obtained the prognosis-related DECRGs through univariate regression analysis.LASSO and multivariate COX regression analyses of these DECRGs yielded four genes that were used to construct the signature. Next, we use ROC curves to evaluate the performance of signatures. The tumor microenvironment, immune infiltration, tumor mutation load, half-maximum suppression concentration, and immunotherapy effects were also compared between the low-risk and high-risk groups. Finally, we analyzed the expression level, prognosis, and immune infiltration correlation on the four genes that constructed the model.
Four DECRGs s were used to construct the signature. The ROC curves indicated that signature can better assess the prognosis of HCC patients. Patients were grouped according to the signature risk score. Patients in the low-risk group had a significantly longer survival time than those in the high-risk group. Furthermore, the tumor mutation burden (TMB) values were associated with the risk score and the higher-risk group had a higher proportion of TP53 mutations than the low-risk group.ESTIMATE analysis showed significant differences in stromal scores between the two groups.N6-methyladenosine (m6A) and multiple immune checkpoints were expressed at higher levels in the high-risk group. Then, we found that signature score correlated with chemotherapeutic drug sensitivity and immunotherapy efficacy in HCC patients. Finally, we further confirmed that the four DECRGs genes were associated with the prognosis of HCC through external validation.
We studied from the cuproptosis perspective and developed a new prognostic feature to predict the prognosis of HCC patients. This signature with good performance will help physicians to evaluate the overall prognosis of patients and may provide new ideas for clinical decision-making and treatment strategies.
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