Analysis and Research on the Relationship between Oral Microorganisms and Alzheimer's Disease.

Background: The common neurodegenerative disease among the elderly is Alzheimer's disease, which in severe cases can affect the quality of life of patients and their families. It has been reported that oral microorganisms are involved in the progression of Alzheimer's disease. Objective: To analyze the relationship between oral microorganisms and Alzheimer's disease. Methods: The oral microbial population, a comprehensive analysis of relevant literature was conducted. Immunofluorescence was adopted to assess albumin deposition in the cerebral cortex of mice. Western blot was used to detect expression level of CYP46 in mouse brain. Results: It can be concluded that the population of oral microorganisms includes bacteria, viruses, fungi, and spirochetes, which can cause various oral diseases. They can enter the human brain through the blood and surrounding nerves, leading to permeability increase of the blood-brain barrier and neuroimmune related inflammation. They will participate in and worsen the pathological process of Alzheimer's disease, leading to damage to neurons and cerebral blood vessels. The intervention methods for oral microbiota population include vaccination and phage therapy. Vaccines provide suitable treatment methods for periodontal disease, and phage therapy is a new method for controlling oral infections. At the same time, postoperative patients with oral diseases can use gel containing ethanol extract of Brazilian green propolis to ensure oral hygiene. In the rat blood-brain barrier model, porphyromonas gingivalis bacteremia enhanced barrier permeability, and immunofluorescence showed an increase in albumin deposition in the rat cerebral cortex. The expression of cytochrome P450 46A1 (CYP46A1) enzyme in the brain of Alzheimer's disease mice aged 24-56 weeks after long-term administration of SLAB51 increased. Conclusion: The elderly population should develop good living habits, maintain a clean mouth, and adjust the oral environment through methods such as oral and Alzheimer's disease promotion, combined with medication treatment.

The emerging roles of hydrogen sulfide in ferroptosis.

SIGNIFICANCE: Ferroptosis, a form of regulated cell death characterized by a large amount of lipid peroxidation-mediated membrane damage, joins the evolution of multisystem diseases. For instance, neurodegenerative diseases, chronic obstructive pulmonary disease and acute respiratory distress syndrome, osteoporosis and osteoarthritis, and so on. Since being identified as the third gasotransmitter in living organisms, the intricate role of hydrogen sulfide (H2S) in ferroptosis has emerged at the forefront of research. RECENT ADVANCES: The discovery of novel targets in the relevant metabolic pathways, including transferrin receptor 1, cystine/glutamate antiporter, and others, coupled with the exploration of new signaling pathways, particularly the p53 signaling pathway and the nitric oxide / nuclear factor erythroid 2-related factor 2 signaling pathway, and so on. Many diseases such as emphysema and airway inflammation, myocardial diseases, endothelial dysfunction in aging arteries, and traumatic brain injury have recently been found to be alleviated directly by H2S inhibition of ferroptosis. Safe, effective, and tolerable novel H2S donors have been developed and have shown promising results in phase I clinical trials. CRITICAL ISSUES: Complicated crosstalk between ferroptosis signaling pathway and oncogenic factors results in the risk of cancer when inhibiting ferroptosis. Notably, targeted delivery of H2S is still a challenging task. FUTURE DIRECTIONS: Discovering more reliable and stable novel H2S donors and achieving their targeted delivery will enable further clinical trials for diseases associated with ferroptosis inhibition by H2S, determining their safety, efficacy, and tolerance.

Effect of Persistent Salt Stress on the Physiology and Anatomy of Hybrid Walnut (Juglans major × Juglans regia) Seedlings.

Soil salinization has become one of the major problems that threaten the ecological environment. The aim of this study is to explore the mechanism of salt tolerance of hybrid walnuts (Juglans major × Juglans regia) under long-term salt stress through the dynamic changes of growth, physiological and biochemical characteristics, and anatomical structure. Our findings indicate that (1) salt stress inhibited seedling height and ground diameter increase, and (2) with increasing salt concentration, relative water content (RWC) decreased, and proline (Pro) and soluble sugar (SS) content increased. The Pro content reached a maximum of 549.64 µg/g on the 42nd day. The increase in superoxide dismutase (SOD) activity (46.80-117.16%), ascorbate peroxidase (APX) activity, total flavonoid content (TFC), and total phenol content (TPC) under salt stress reduced the accumulation of malondialdehyde (MDA). (3) Increasing salt concentration led to increases and subsequent decreases in the thickness of palisade tissues, spongy tissues, leaves, and leaf vascular bundle diameter. Upper and lower skin thickness, root periderm thickness, root diameter, root cortex thickness, and root vascular bundle diameter showed different patterns of change at varying stress concentrations and durations. Overall, the study concluded that salt stress enhanced the antireactive oxygen system, increased levels of osmotic regulators, and low salt concentrations promoted leaf and root anatomy, but that under long-term exposure to high salt levels, leaf anatomy was severely damaged. For the first time, this study combined the anatomical structure of the vegetative organ of hybrid walnut with physiology and biochemistry, which is of great significance for addressing the challenge of walnut salt stress and expanding the planting area.

Role of hydrogen sulfide in dermatological diseases.

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.

Nuclear proteins and diabetic retinopathy: a review.

Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

Targeting colorectal cancer at the level of nuclear pore complex.

BACKGROUND: Nuclear pore complexes (NPCs) are the architectures entrenched in nuclear envelop of a cell that regulate the nucleo-cytoplasmic transportation of materials, such as proteins and RNAs for proper functioning of a cell. The appropriate localization of proteins and RNAs within the cell is essential for its normal functionality. For such a complex transportation of materials across the NPC, around 60 proteins are involved comprising nucleoporins, karyopherins and RAN system proteins that play a vital role in NPC's structure formation, cargo translocation across NPC, and cargoes' rapid directed transportation respectively. In various cancers, the structure and function of NPC is often exaggerated, following altered expressions of its nucleoporins and karyopherins, affecting other proteins of associated signaling pathways. Some inhibitors of karyopherins at present, have potential to regulate the altered level/expression of these karyopherin molecules. AIM OF REVIEW: This review summarizes the data from 1990 to 2023, mainly focusing on recent studies that illustrate the structure and function of NPC, the relationship and mechanisms of nucleoporins and karyopherins with colorectal cancer, as well as therapeutic values, in order to understand the pathology and underlying basis of colorectal cancer associated with NPC. This is the first review to our knowledge elucidating the detailed updated studies targeting colorectal cancer at NPC. The review also aims to target certain karyopherins, Nups and their possible inhibitors and activators molecules as a therapeutic strategy. KEY SCIENTIFIC CONCEPTS OF REVIEW: NPC structure provides understanding, how nucleoporins and karyopherins as key molecules are responsible for appropriate nucleocytoplasmic transportation. Many studies provide evidences, describing the role of disrupted nucleoporins and karyopherins not only in CRC but also in other non-hematological and hematological malignancies. At present, some inhibitors of karyopherins have therapeutic potential for CRC, however development of more potent inhibitors may provide more effective therapeutic strategies for CRC in near future.

Regulatory roles of N6-methyladenosine (m6A) methylation in RNA processing and non-communicable diseases.

Post-transcriptional RNA modification is an emerging epigenetic control mechanism in cells that is important in many different cellular and organismal processes. N6-methyladenosine (m6A) is one of the most prevalent, prolific, and ubiquitous internal transcriptional alterations in eukaryotic mRNAs, making it an important topic in the field of Epigenetics. m6A methylation acts as a dynamical regulatory process that regulates the activity of genes and participates in multiple physiological processes, by supporting multiple aspects of essential mRNA metabolic processes, including pre-mRNA splicing, nuclear export, translation, miRNA synthesis, and stability. Extensive research has linked aberrations in m6A modification and m6A-associated proteins to a wide range of human diseases. However, the impact of m6A on mRNA metabolism and its pathological connection between m6A and other non-communicable diseases, including cardiovascular disease, neurodegenerative disorders, liver diseases, and cancer remains in fragmentation. Here, we review the existing understanding of the overall role of mechanisms by which m6A exerts its activities and address new discoveries that highlight m6A's diverse involvement in gene expression regulation. We discuss m6A deposition on mRNA and its consequences on degradation, translation, and transcription, as well as m6A methylation of non-coding chromosomal-associated RNA species. This study could give new information about the molecular process, early detection, tailored treatment, and predictive evaluation of human non-communicable diseases like cancer. We also explore more about new data that suggests targeting m6A regulators in diseases may have therapeutic advantages.

Functional role of autophagy in testicular and ovarian steroidogenesis.

Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies.

Exploring the impact of hydrogen sulfide on hematologic malignancies: A review.

Hydrogen sulfide (H2S) is one of the three most crucial gaseous messengers in the body. The discovery of H2S donors, coupled with its endogenous synthesis capability, has sparked hope for the treatment of hematologic malignancies. In the last decade, the investigation into the impact of H2S has expanded, particularly within the fields of cardiovascular function, inflammation, infection, and neuromodulation. Hematologic malignancies refer to a diverse group of cancers originating from abnormal proliferation and differentiation of blood-forming cells, including leukemia, lymphoma, and myeloma. In this review, we delve deeply into the complex interrelation between H2S and hematologic malignancies. In addition, we comprehensively elucidate the intricate molecular mechanisms by which both H2S and its donors intricately modulate the progression of tumor growth. Furthermore, we systematically examine their impact on pivotal aspects, encompassing the proliferation, invasion, and migration capacities of hematologic malignancies. Therefore, this review may contribute novel insights to our understanding of the prospective therapeutic significance of H2S and its donors within the realm of hematologic malignancies.

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Recent Insights into the Roles of PEST-Containing Nuclear Protein.

PEST-containing nuclear protein (PCNP), a short-lived small nuclear protein with 178 amino acids, is a nuclear protein containing two PEST sequences. PCNP is highly expressed in several malignant tumors such as cervical cancer, rectal cancer, and lung cancer. It is also associated with cell cycle regulation and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Wnt signaling pathways during tumor growth. The present article discuss how PCNP regulates the PI3K/AKT/mTOR and Wnt signaling pathways and related proteins, and the ubiquitination of PCNP regulates tumor cell cycle as well as the progress of the application of PCNP in the pathophysiology and treatment of colon cancer, human ovarian cancer, thyroid cancer, lung adenocarcinoma and oral squamous cell carcinoma. The main relevant articles were retrieved from PubMed, with keywords such as PEST-containing nuclear protein (PCNP), cancer (tumor), and signaling pathways as inclusion/exclusion criteria. Relevant references has been included and cited in the manuscript.

RIPK3 signaling and its role in regulated cell death and diseases.

Receptor-interacting protein kinase 3 (RIPK3), a member of the receptor-interacting protein kinase (RIPK) family with serine/threonine protein kinase activity, interacts with RIPK1 to generate necrosomes, which trigger caspase-independent programmed necrosis. As a vital component of necrosomes, RIPK3 plays an indispensable role in necroptosis, which is crucial for human life and health. In addition, RIPK3 participates in the pathological process of several infections, aseptic inflammatory diseases, and tumors (including tumor-promoting and -suppressive activities) by regulating autophagy, cell proliferation, and the metabolism and production of chemokines/cytokines. This review summarizes the recent research progress of the regulators of the RIPK3 signaling pathway and discusses the potential role of RIPK3/necroptosis in the aetiopathogenesis of various diseases. An in-depth understanding of the mechanisms and functions of RIPK3 may facilitate the development of novel therapeutic strategies.

[Association Between Dietary Diversity and Caregiver Self-Efficacy for Complementary Feeding Among Infants and Young Children Aged 6-23 Months in Rural Nanchong City,Sichuan Province].

Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy. Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for complementary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diversity and caregiver self-efficacy for complementary feeding of infants and young children. Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56%(474/770) for all the infants and young children and 45.00%(108/240),69.16%(287/415),and 68.70%(79/115) for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respectively.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing factor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR=1.42,95%CI=1.17-1.73,P<0.001). Conclusion The dietary diversity for infants and young children in rural Nanchong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.

The potential role of hydrogen sulfide in cancer cell apoptosis.

For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

The regulating mechanism of salt tolerance of black walnut seedlings was revealed by the physiological and biochemical integration analysis.

Salt stress is an important abiotic stress that seriously affects plant growth. In order to research the salt tolerance of walnut rootstocks so as to provide scientific basis for screening salt-tolerant walnut rootstocks, two kinds of black walnut seedlings, Juglans microcarpa L. (JM) and Juglans nigra L. (JN), were treated under salt stress with different concentrations of NaCl (0, 50, 100, and 200 mM) and the growth situation of seedlings were observed. The physiological indexes of JM and JN seedlings were also measured in different days after treatment. Our study showed salt stress inhibited seedlings growth and limited biomass accumulation. Walnut mainly increased osmotic adjustment ability by accumulation Pro and SS. Furthermore, with the duration of treatment time increased, SOD and APX activities decreased, TPC and TFC contents increased. Walnut accumulated Na mostly in roots and transported more K and Ca to aboveground parts. The growth and physiological response performance differed between JM and JN, specifically, the differences occurred in the ability to absorb minerals, regulate osmotic stress, and scavenge ROS. Salt tolerance of JM and JN was assessed by principal component analysis (PCA) and resulted in JN > JM. In conclusion, our results indicated that JN has higher salt tolerance than JM, and JN might be used as a potential germplasm resource for the genetic breeding of walnuts.

Monkeypox Entry and Emergence Preparation in Pakistan.

Monkeypox (Mpox) is a virus that first emerged in Africa in 1970 [...].

Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells.

BACKGROUND: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. METHODS: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-ß-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. RESULTS: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. CONCLUSION: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration.

Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer's disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.

Hydrogen sulfide-induced post-translational modification as a potential drug target.

Hydrogen sulfide (H2S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H2S has been increasing. H2S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H2S in a variety of physiological processes. Current studies have shown that H2S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H2S on physiological and pathological processes, looking forward to providing guidance for subsequent research.

The role of microRNAs in depression.

Major depressive disorder (MDD) is a psychiatric disorder with increasing prevalence worldwide. It is a leading cause of disability and suicide, severely affecting physical and mental health. However, the study of depression remains at an exploratory stage in terms of diagnostics and treatment due to the complexity of its pathogenesis. MicroRNAs are endogenous short-stranded non-coding RNAs capable of binding to the 3'untranslated region of mRNAs. Because of their ability to repress translation process of genes and are found at high levels in brain tissues, investigation of their role in depression has gradually increased recently. This article summarizes recent research progress on the relationship between microRNAs and depression. The microRNAs play a regulatory role in the pathophysiology of depression, involving dysregulation of monoamines, abnormalities in neuroplasticity and neurogenesis, hyperactivity of the HPA axis, and dysregulation of inflammatory responses. These microRNAs might provide new clue for the diagnosis and treatment of MDD, and the development of antidepressant drugs.