Efficacy and safety of stem cell therapy in cerebral palsy: A systematic review and meta-analysis

Aim: Although the efficacy and safety of stem cell therapy for cerebral palsy has been demonstrated in previous studies, the number of studies is limited and the treatment protocols of these studies lack consistency. Therefore, we included all relevant studies to date to explore factors that might influence the effectiveness of treatment based on the determination of safety and efficacy.Methods: The data source includes PubMed/Medline, Web of Science, EMBASE, Cochrane Library, from inception to 2 January 2022. Literature was screened according to the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the outcome indicators of each study were extracted for combined analysis.Results: 9 studies were included in the current analysis. The results of the pooled analysis showed that the improvements in both primary and secondary indicators except for Bayley Scales of Infant and Toddler Development were more skewed towards stem cell therapy than the control group. In the subgroup analysis, the results showed that stem cell therapy significantly increased Gross Motor Function Measure (GMFM) scores of 3, 6, and 12 months. Besides, improvements in GMFM scores were more skewed toward umbilical cord mesenchymal stem cells, low dose, and intrathecal injection. Importantly, there was no significant difference in the adverse events (RR = 1.13; 95% CI = [0.90, 1.42]) between the stem cell group and the control group.Conclusion: The results suggested that stem cell therapy for cerebral palsy was safe and effective. Although the subgroup analysis results presented guiding significance in the selection of clinical protocols for stem cell therapy, high-quality RCTs validations are still needed

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition

Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer

Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment in vivo, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, p=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A>G, m.3970 C>T, m.4071 C>T, m.4086 C>T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data

Population Genetic Structure of Peninsular Malaysia Malay Sub-Ethnic Groups

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia

Magneto-controlled potentiometric assay for E. coli based on cleavage of peptide by outer-membrane protease T

Rapid, sensitive and reliable Escherichia coli (E. coli) detection and identification are critically important to protect public health. Here, we describe a magneto-controlled potentiometric assay for specific detection of E. coli cells by making use of the E. coli outer-membrane protease T (OmpT). OmpT is an endopepti-dase that specifically cleaves peptide at dibasic sites. A rationally designed peptide serving as both OmpT substrate and potentiometric signal reporter was immobilized on magnetic beads. The rapid accumu-lation and extraction of peptide-functionalized magnetic beads on a polymeric membrane doped with an ion exchanger can be achieved using a magnetic force. The magnetic-field-assisted extraction of the peptide into the polymeric membrane ion-sensitive sensor, as confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, can lead to a rapid, stable and reproducible potential change. OmpT is capable of cleaving the positively charged peptide on the magnetic beads, thus resulting in charge density change. The change in charge density and subsequently the potential change can be readily detected and used for quantification of E. coli at levels down to 5.0 x 10(-3) CFU mL(-1). This work provides a versatile, rapid and reliable potentiometric method for E. coli detection. (C) 2021 Elsevier Ltd. All rights reserved

Peptide-Driven Assembly of Magnetic Beads for Potentiometric Sensing of Bacterial Enzyme at a Subcellular Level

Bacterial enzymes with different subcellular localizations play a critical ecological role in biogeochemical processing. However, precisely quantifying enzymes localized at certain subcellular levels, such as extracellular enzymes, has not yet been fully realized due to the complexity and dynamism of the bacterial outer membrane. Here we present a magneto-controlled potentiometric sensing platform for the specific detection of extracellular enzymatic activity. Alkaline phosphatase (ALP), which is one of the crucial hydrolytic enzymes in the ocean, was selected as the target enzyme. Magnetic beads functionalized with an ALP-responsive self-assembled peptide (GGGGGFFFpYpYEEE, MBs-peptides) prevent negatively charged peptides from entering the bacterial outer membrane, thereby enabling direct potentiometric sensing of extracellular ALP both attached to the bacterial cell surface and released into the surrounding environment. The dephosphorylation-triggered assembly of peptide-coupled magnetic beads can be directly and sensitively measured by using a magneto-controlled sensor. In this study, extracellular ALP activity of Pseudomonas aeruginosa at concentrations ranging from 10 to 1.0 x 10(5) CFU mL(-1) was specifically and sensitively monitored. Moreover, this magneto-controlled potentiometric method enabled a simple and accurate assay of ALP activity across different subcellular localizations

Rapid antibiotic screening based on E. coli apoptosis using a potentiometric sensor array

Phenotypic antimicrobial susceptibility testing enables reliable antibiotic screening but requires multiple strategies to identify each phenotypic change induced by different bactericidal mechanisms. Bacteria apoptosis with typical phenotypic features has never been explored for antibiotic screening. Herein, we developed an antibiotic screening method based on the measurement of antibiotic-induced phosphatidylserine (PS) exposure of apoptotic bacteria. Phosphatidylserine externalization of E. coli that can be widely used as an apoptosis marker for antibiotics with different antibacterial mechanisms was explored. A positively charged PS-binding peptide was immobilized on magnetic beads (MBs) to recognize and capture apoptotic E. coli with PS externalization. Apoptotic E. coli binding led to the charge or charge density change of MBs-peptide, resulting in a potential change on a magneto-controlled polymeric membrane potentiometric sensor. Based on the detection of apoptotic E. coli killed by antibiotics, antibiotic screening for different classes of antibiotics and silver nanoparticles was achieved within 1.5 h using a potentiometric sensor array. This approach enables sensitive, general, and timesaving antibiotic screening, and may open up a new path for antibiotic susceptibility testing

Rapid Antibiotic Screening Based on Bacteria Apoptosis Using Potentiometric Sensor Array

Phenotypic antimicrobial susceptibility testing that identifies the phenotypic feature differences of bacteria after incubation with antibiotics enables reliable antibiotics screening but is restricted by bacterial proliferation rate. Here, a magneto-controlled potentiometric sensors array was developed for rapid antibiotic screening based on direct detection of apoptotic bacteria. Phosphatidylserine (PS)-binding peptide serving as bioreceptor and signal transducer was immobilized on magnetic beads (MBs-peptide), and could selectively capture apoptotic bacteria killed by antibiotics. Apoptotic bacteria binding-induced charge density change of MBs-peptide resulted in a potential change on a magneto-controlled polymeric membrane potentiometric sensor. Based on the apoptotic bacteria detection, antimicrobial activities of micrograms per milliliter antibiotics could be evaluated within 1.5 h, which were hardly achieved by current methods. In addition, the antibacterial ability of different antibiotics could be evaluated simultaneously using a potentiometric sensors array. This approach enables sensitive, general, and time-saving antibiotic screening, and may open up a new path for antibiotic susceptibility testing. © 2023, The Authors. All rights reserved