International Journal of Molecular Sciences最新文献

Protocatechuate acid (PCA) is a phenolic acid naturally synthesized by various organisms. Protocatechuic acid is synthesized by plants for physiological, metabolic functions, and self-defense, but extraction from plants is less efficient compared to the microbial culture process. The microbial synthesis of protocatechuic acid is sustainable and, due to its high yield, can save energy consumption when producing the same amount. To enhance PCA production using Corynebacterium glutamicum, a statistical optimization of the production medium was performed using full factorial design, the steepest ascent method, and the response surface method. The optimized production medium enabled a PCA production of over 5 g/L in a 72 h batch culture. However, PCA cytotoxicity affected the strain growth and PCA production rate, with an inhibitory concentration of approximately 5 g/L in the fermentation broth. Finally, continuous fermentation was operated for 150 h in the steady-state mode, maintaining the concentration of PCA below 5 g/L. The optimization method established in this study successfully increased PCA production levels, and the findings presented herein are anticipated to contribute to the industrialization of PCA production using C. glutamicum.

The size of viral genomes is limited, thus the majority of encoded proteins possess multiple functions. The main function of tobamoviral movement protein (MP) is to perform plasmodesmata gating and mediate intercellular transport of the viral RNA. MP is a remarkable example of a protein that, in addition to the initially discovered and most obvious function, carries out numerous activities that are important both for the manifestation of its key function and for successful and productive infection in general. Briefly, MP binds the viral genome, delivers it to the plasmodesmata (PD) and mediates its intercellular transfer. To implement the transport function, MP interacts with diverse cellular factors. Each of these cellular proteins has its own function, which could be different under normal conditions and upon viral infection. Here, we summarize the data available at present on the plethora of cellular factors that were identified as tobamoviral MP partners and analyze the role of these interactions in infection development.

From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca²⁺ transfers. In addition, from around the eighth week of gestation, increasing amounts of calcium must be routed directly from maternal blood to the foetus for bone mineralisation through a flow-through system, which does not impact the intracellular Ca²⁺ concentration. These different processes are mediated by numerous membrane-sited Ca²⁺ channels, transporters, and exchangers. Understanding the mechanisms is essential to direct interventions to optimise foetal development and postnatal bone health and to protect the mother and foetus from pre-eclampsia. Ethical issues limit the availability of human foetal tissue for study. Our insight into the processes of placental Ca²⁺ handling is advancing rapidly, enabled by developing genetic, analytical, and computer technology. Because of their diverse sources, the reports of new findings are scattered. This review aims to pull the data together and to highlight areas of uncertainty. Areas needing clarification include trafficking, membrane expression, and recycling of channels and transporters in the placental microvilli; placental metabolism of vitamin D in gestational diabetes and pre-eclampsia; and the vascular effects of increased endothelial Orai expression by pregnancy-specific beta-1-glycoproteins PSG1 and PSG9.

Immunotherapies aimed at preserving residual beta cell function in type 1 diabetes have been successful, although the effect has been limited, or raised safety concerns. Transient effects often observed may necessitate redosing to prolong the effect, although this is not always feasible or safe. Treatment with intralymphatic GAD-alum has been shown to be tolerable and safe in persons with type 1 diabetes and has shown significant efficacy to preserve C-peptide with associated clinical benefit in individuals with the human leukocyte antigen DR3DQ2 haplotype. To further explore the feasibility and advantages of redosing with intralymphatic GAD-alum, six participants who had previously received active treatment with intralymphatic GAD-alum and carried HLA DR3-DQ2 received one additional intralymphatic dose of 4 μg GAD-alum in the pilot trial DIAGNODE-B. The participants also received 2000 U/day vitamin D (Calciferol) supplementation for two months, starting one month prior to the GAD-alum injection. During the 12-month follow-up, residual beta cell function was estimated with Mixed-Meal Tolerance Tests, and clinical and immune responses were observed. C-peptide decreased minimally, and most patients showed stable HbA1c and IDAA1c. The mean % TIR increased while the mean daily insulin dose decreased at month 12 compared to the baseline. Redosing with GAD-alum seems to be safe and tolerable, and may prolong the disease modification elicited by the original GAD-alum treatment.

In recent years, circular RNAs (circRNAs) have garnered significant attention due to their unique structure and function, positioning them as promising candidates for next-generation vaccines. The circRNA vaccine, as an RNA vaccine, offers significant advantages in preventing infectious diseases by serving as a vector for protein expression through non-canonical translation. Notably, circRNA vaccines have demonstrated enduring antigenic expression and generate a larger percentage of neutralizing antibodies compared to mRNA vaccines administered at the same dosage. Furthermore, circRNA vaccines can elicit robust cellular and humoral immunity, indicating their potential for tumor vaccine development. However, certain challenges must be addressed to facilitate the widespread use of circRNA vaccines in both infectious disease prevention and tumor treatment. These challenges include the low efficiency of linear RNA circularization, the suboptimal targeting of delivery systems, and the assessment of potential side effects. This work aims to describe the characteristics and functions of circRNAs, elucidate the mechanism behind circRNA vaccines, and discuss their applications in the prevention of infectious diseases and the treatment of tumors, along with their potential future applications.

Garlic (Allium sativum L.) is one of the oldest known useful plants, valued for thousands of years. This plant contains many biologically active compounds, including polyphenols, sterols, cysteine-sulfoxides, carbohydrates, proteins, and amino acids. The aim of our study was to compare the antioxidant potential, cytotoxicity, and apoptosis induction properties of four garlic cultivars-Harnaś, Ornak, Violeta, and Morado-in human squamous carcinoma (SCC-15) cells, colon adenocarcinoma (CACO-2) cells, and normal fibroblasts (BJ). Additionally, we investigated the mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARγ), microtubule-associated protein 1 light chain 3 (LC3A), superoxide dismutase 1 (SOD1), and catalase (CAT) after treatment with the studied garlic extracts. Our study demonstrated that high ROS production was correlated with the strong toxicity of the garlic extracts. All studied extracts produced a lesser increase in ROS in normal BJ fibroblasts and were less toxic to these cells. The expression patterns of PPARγ, LC3A, SOD1, and CAT, along with chromatographic analysis, suggest differing mechanisms among the garlic cultivars. The highest levels of catechin, a known PPARγ agonist, were detected in the Harnaś (3.892 µg/mL) and Ornak (3.189 µg/mL) cultivars. A high catechin content was correlated with similar changes in PPARγ and related SOD1 and LC3A. Our findings showed the health-promoting and anticancer properties of garlic. However, we could not definitively identify which polyphenol or how it is involved in PPARγ activation. Further studies are required to elucidate the role of PPARγ in the mechanism of action of garlic extracts.

The interplay between the cytokine network and antipsychotic treatment in schizophrenia remains poorly understood. This study aimed to investigate the impact of psychotropic medications on serum levels of IFN-γ, IL-4, TGF-β1, IL-17, and BAFF, and to explore their relationship with psychopathological features. We recruited 63 patients diagnosed with schizophrenia in the acute phase, all of whom were either drug-naïve or had been drug-free for at least three months. Serum levels of IL-4, IFN-γ, TGF-β1, IL-17, and BAFF were measured at baseline and after six months of antipsychotic treatment. The severity of symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms (SANS). Fifty-two patients completed the six-month follow-up for immunoassay analysis. Antipsychotic treatment led to a significant decrease in serum levels of IFN-γ, TGF-β1, and IL-17, alongside a significant increase in BAFF levels. Changes in IFN-γ were positively correlated with SANS scores and negatively correlated with Global Assessment of Functioning (GAF) scores. Changes in TGF-β1 were negatively correlated with GAF scores. Changes in BAFF were negatively correlated with SAPS scores. Multivariable regression models were used to explore the association between cytokine level changes (IL-17, BAFF, IFN-γ, and TGF-β1) and independent variables, including demographic (gender, age), behavioral (tobacco use), clinical (schizophrenia type, disease course, date of onset, prior treatment), and biological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) factors, as well as standardized assessment scores. No significant associations were found, except for a significant negative correlation between TGF-β1 changes and GAF scores, as well as a positive correlation with age. Interestingly, advanced statistical analyses revealed that only changes in IL-17 and BAFF levels were significantly associated with antipsychotic treatment. Our findings suggest that antipsychotic drugs exert both pro- and anti-inflammatory effects on the cytokine network. The observed modulation of IL-17 and BAFF highlights their potential as future therapeutic targets in schizophrenia.

Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides a comprehensive analysis of the effects of PSMs on mitochondrial health, with particular emphasis on their therapeutic potential. Emerging evidence shows that these metabolites improve mitochondrial function by reducing oxidative stress, promoting mitochondrial biogenesis, and regulating key processes such as apoptosis and mitophagy. Mitochondrial dysfunction, a hallmark of many pathologies, including neurodegenerative disorders, cardiovascular diseases, and metabolic syndrome, has been shown to benefit from the protective effects of PSMs. Recent studies show that PSMs can improve mitochondrial dynamics, stabilise mitochondrial membranes, and enhance bioenergetics, offering significant promise for the prevention and treatment of mitochondrial-related diseases. The molecular mechanisms underlying these effects, including modulation of key signalling pathways and direct interactions with mitochondrial proteins, are discussed. The integration of PSMs into therapeutic strategies is highlighted as a promising avenue for improving treatment efficacy while minimising the side effects commonly associated with synthetic drugs. This review also highlights the need for future research to elucidate the specific roles of individual PSMs and their synergistic interactions within complex plant matrices, which may further optimise their therapeutic utility. Overall, this work provides valuable insights into the complex role of PSMs in mitochondrial health and their potential as natural therapeutic agents targeting mitochondrial dysfunction.

Adipose tissue of obese people secretes a number of adipokines, including adiponectin and resistin, which have an antagonistic effect on the human metabolism, influencing the pathogenesis of many diseases based on low-grade inflammation. Body composition analysis using bioelectrical impedance analysis (BIA) was performed in 84 adults with obesity, i.e., body mass index (BMI) greater than or equal to 30 kg/m². Serum was collected to analyze the concentration of adiponectin (ApN) and resistin. The subjects additionally completed a food frequency questionnaire FFQ-6 and a three-day food diary. Adiponectin-resistin index (AR index) was calculated. The results show a positive correlation between resistin levels and BMI and subcutaneous fat content. AR index value was also positively associated with the amount of adipose tissue and body mass. Adiponectin level in the serum of the studied individuals decreased with the content of lean tissue. Adiponectin level also decreased with the amount of carbohydrates, amount of starch, and glycemic load of the diet. Resistin decreased in patients who frequently consumed white pasta and red meat, while AR index was positively associated with the amount of white rice and saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) consumed but negatively associated with the frequent consumption of carbohydrates, including starch. Physical activity was negatively correlated with adiponectin levels and AR index. We concluded that body composition significantly influenced serum resistin and adiponectin concentrations the AR index. Dietary components also had a significant effect.

With the rapid advancement of high-throughput sequencing technologies, whole genome sequencing (WGS) has emerged as a crucial tool for studying genetic variation and population structure. Utilizing population genomics tools to analyze resequencing data allows for the effective integration of selection signals with population history, precise estimation of effective population size, historical population trends, and structural insights, along with the identification of specific genetic loci and variations. This paper reviews current whole genome sequencing technologies, detailing primary research methods, relevant software, and their advantages and limitations within population genomics. The goal is to examine the application and progress of resequencing technologies in this field and to consider future developments, including deep learning models and machine learning algorithms, which promise to enhance analytical methodologies and drive further advancements in population genomics.