Search

Cryopreservation is a crucial technique for the long-term ex situ conservation of plant genetic resources, particularly in the context of global biodiversity decline. This process entails freezing biological material at ultra-low temperatures using liquid nitrogen, which effectively halts metabolic activities and preserves plant tissues over extended periods. Over the past seven decades, a plethora of techniques for cryopreserving plant materials have been developed. These include slow freezing, vitrification, encapsulation dehydration, encapsulation–vitrification, droplet vitrification, cryo-plates, and cryo-mesh techniques. A key challenge in the advancement of cryopreservation lies in our ability to understand the molecular processes underlying plant freezing tolerance. These mechanisms include cold acclimatization, the activation of cold-responsive genes through pathways such as the ICE–CBF–COR cascade, and the protective roles of transcription factors, non-coding RNAs, and epigenetic modifications. Furthermore, specialized proteins, such as antifreeze proteins (AFPs) and late embryogenesis abundant (LEA) proteins, play crucial roles in protecting plant cells during freezing and thawing. Despite its potential, cryopreservation faces significant challenges, particularly in standardizing protocols for a wide range of plant species, especially those from tropical and subtropical regions. This review highlights the importance of ongoing research and the integration of omics technologies to improve cryopreservation techniques, ensuring their effectiveness across diverse plant species and contributing to global efforts regarding biodiversity conservation. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a heavy metal element with a wide range of hazards and severe biotoxicity. Since Cd can be easily accumulated in the edible parts of plants, the exposure of humans to Cd is mainly through the intake of Cd-contaminated food. However, the intestinal responses to Cd exposure are not completely characterized. Herein, we simulated laboratory and environmental Cd exposure by feeding the piglets with CdCl2-added rice and Cd-contaminated rice (Cdcr) contained diet, as piglets show anatomical and physiological similarities to humans. Subsequent analysis of the metal element concentrations showed that exposure to the two types of Cd significantly increased Cd levels in piglets. After verifying the expression of major Cd transporters by Western blots, multi-omics further expanded the possible transporters of Cd and found Cd exposure causes wide alterations in the metabolism of piglets. Of significance, CdCl2 and Cdcr exhibited different body distribution and metabolic rewiring, and Cdcr had stronger carcinogenic and diabetes-inducing potential. Together, our results indicate that CdCl2 had a significant difference compared with Cdcr, which has important implications for a more intense study of Cd toxicity. [ABSTRACT FROM AUTHOR]

The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death. The present review provides an updated summary of necrosis subtypes and discusses their potential roles in neurodegenerative cell death. Among numerous necrosis subtypes, including necroptosis, paraptosis, ferroptosis, and pyroptosis, transcriptional repression-induced atypical cell death (TRIAD) has been identified as a potential mechanism of neuronal cell death. TRIAD is induced by functional deficiency of TEAD-YAP and self-amplifies via the release of HMGB1. TRIAD is a feasible potential mechanism of neuronal cell death in Alzheimer's disease and other neurodegenerative diseases. In addition to induction of cell death, HMGB1 released during TRIAD activates brain inflammatory responses, which is a potential link between neurodegeneration and neuroinflammation. [ABSTRACT FROM AUTHOR]

Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels. Brain disease, especially ischemic stroke, epilepsy, and traumatic brain injury, triggers the dysregulation of ionic gradients and promotes the excessive release of neuro-transmitters and zinc. The divalent metal cation zinc is highly distributed in the brain and is specifically located in the pre-synaptic vesicles as free ions, usually existing in cytoplasm bound with metallothionein. Although adequate zinc is essential for regulating diverse physiological functions, the brain-disease-induced excessive release and translocation of zinc causes cell damage, including oxidative stress, apoptotic cascades, and disturbances in energy metabolism. Therefore, the regulation of zinc homeostasis following brain disease is critical for the prevention of brain damage. In this review, we summarize recent experimental research findings regarding how TRP channels (mainly TRPC and TRPM) and zinc are regulated in animal brain-disease models of global cerebral ischemia, epilepsy, and traumatic brain injury. The blockade of zinc translocation via the inhibition of TRPC and TRPM channels using known channel antagonists, was shown to be neuroprotective in brain disease. The regulation of both zinc and TRP channels may serve as targets for treating and preventing neuronal death. [ABSTRACT FROM AUTHOR]

Cadmium (Cd2+) exposure induces chronic kidney disease and renal cancers, which originate from injury and cancerization of renal tubular cells. Previous studies have shown that Cd2+ induced cytotoxicity by disrupting the intracellular Ca2+ homeostasis that is physically regulated by the endoplasmic reticulum (ER) Ca2+ store. However, the molecular mechanism of ER Ca2+ homeostasis in Cd2+-induced nephrotoxicity remains unclear. In this study, our results firstly revealed that the activation of calcium-sensing receptor (CaSR) by NPS R-467 could protect against Cd2+ exposure-induced cytotoxicity of mouse renal tubular cells (mRTEC) by restoring ER Ca2+ homeostasis through the ER Ca2+ reuptake channel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). Cd2+-induced ER stress and cell apoptosis were effectively abrogated by SERCA agonist CDN1163 and SERCA2 overexpression. In addition, in vivo, and in vitro results proved that Cd2+ reduced the expressions of SERCA2 and its activity regulator phosphorylation phospholamban (p-PLB) in renal tubular cells. Cd2+-induced SERCA2 degradation was suppressed by the treatment of proteasome inhibitor MG132, which suggested that Cd2+ reduced SERCA2 protein stability by promoting the proteasomal protein degradation pathway. These results suggested that SERCA2 played pivotal roles in Cd2+-induced ER Ca2+ imbalance and stress to contribute to apoptosis of renal tubular cells, and the proteasomal pathway was involved in regulating SERCA2 stability. Our results proposed a new therapeutic approach targeting SERCA2 and associated proteasome that might protect against Cd2+-induced cytotoxicity and renal injury. [ABSTRACT FROM AUTHOR]

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required. [ABSTRACT FROM AUTHOR]

Glucose homeostasis is of critical importance for the survival of organisms. It is under hormonal control and often coordinated by the action of kinases and phosphatases. We have previously shown that CK2 regulates insulin production and secretion in pancreatic β-cells. In order to shed more light on the CK2-regulated network of glucose homeostasis, in the present study, a qRT-PCR array was carried out with 84 diabetes-associated genes. After inhibition of CK2, fructose-1,6-bisphosphatase 1 (FBP1) showed a significant lower gene expression. Moreover, FBP1 activity was down-regulated. Being a central enzyme of gluconeogenesis, the secretion of glucose was decreased as well. Thus, FBP1 is a new factor in the CK2-regulated network implicated in carbohydrate metabolism control. [ABSTRACT FROM AUTHOR]

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce cancer-related thrombosis. Here, we discuss the potential function of platelets in regulating cancer progression and summarize the factors and signaling pathways that mediate the cancer cell-platelet interaction. [ABSTRACT FROM AUTHOR]

Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney). [ABSTRACT FROM AUTHOR]

Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC-amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities. [ABSTRACT FROM AUTHOR]

Among the organs in which the environmental pollutant cadmium causes toxicity, the kidney has gained the most attention in recent years. Numerous studies have sought to unravel the exact pathways by which cadmium enters the renal epithelial cells and the mechanisms by which it causes toxicity in the kidney. The purpose of this review is to present the progress made on the mechanisms of cadmium transport in the kidney and the role of transporter proteins in cadmium-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

In the modern process of drug discovery, clinical, functional and chemical proteomics can converge and integrate synergies. Functional proteomics explores and elucidates the components of pathways and their interactions which, when deregulated, lead to a disease condition. This knowledge allows the design of strategies to target multiple pathways with combinations of pathway-specific drugs, which might increase chances of success and reduce the occurrence of drug resistance. Chemical proteomics, by analyzing the drug interactome, strongly contributes to accelerate the process of new druggable targets discovery. In the research area of clinical proteomics, proteome and peptidome mass spectrometry-profiling of human bodily fluid (plasma, serum, urine and so on), as well as of tissue and of cells, represents a promising tool for novel biomarker and eventually new druggable targets discovery. In the present review we provide a survey of current strategies of functional, chemical and clinical proteomics. Major issues will be presented for proteomic technologies used for the discovery of biomarkers for early disease diagnosis and identification of new drug targets. [ABSTRACT FROM AUTHOR]

Tau protein plays a critical role in the assembly, stabilization, and modulation of microtubules, which are important for the normal function of neurons and the brain. In diseased conditions, several pathological modifications of tau protein manifest. These changes lead to tau protein aggregation and the formation of paired helical filaments (PHF) and neurofibrillary tangles (NFT), which are common hallmarks of Alzheimer's disease and other tauopathies. The accumulation of PHFs and NFTs results in impairment of physiological functions, apoptosis, and neuronal loss, which is reflected as cognitive impairment, and in the late stages of the disease, leads to death. The causes of this pathological transformation of tau protein haven't been fully understood yet. In both physiological and pathological conditions, tau interacts with several proteins which maintain their proper function or can participate in their pathological modifications. Interaction partners of tau protein and associated molecular pathways can either initiate and drive the tau pathology or can act neuroprotective, by reducing pathological tau proteins or inflammation. In this review, we focus on the tau as a multifunctional protein and its known interacting partners active in regulations of different processes and the roles of these proteins in Alzheimer's disease and tauopathies. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet–leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet–monocyte and platelet–granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet–leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet–leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk. [ABSTRACT FROM AUTHOR]

Taken with the growing importance of cathepsin-mediated substrate proteolysis in tumor biology and progression, the focus and emphasis placed on therapeutic design and development is coming into fruition. Underpinning this approach is the invariable progression from the direction of fully characterizing cathepsin protease members and their substrate targets, towards targeting such an interaction with tangible therapeutics. The two groups of such substrates that have gained much attention over the years are the pro- and anti- apoptotic protein intermediates from the extrinsic and intrinsic signaling arms of the apoptosis pathway. As proteins that are central to determining cellular fate, some of them present themselves as very favorable candidates for therapeutic targeting. However, considering that both anti- and pro- apoptotic signaling intermediates have been reported to be downstream substrates for certain activated cathepsin proteases, therapeutic targeting approaches based on greater selectivity do need to be given greater consideration. Herein, we review the relationships shared by the cathepsin proteases and the Bcl-2 homology domain proteins, in the context of how the topical approach of adopting 'BH3-mimetics' can be explored further in modulating the relationship between the anti- and pro- apoptotic signaling intermediates from the intrinsic apoptosis pathway and their upstream cathepsin protease regulators. Based on this, we highlight important future considerations for improved therapeutic design. [ABSTRACT FROM AUTHOR]

Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management. [ABSTRACT FROM AUTHOR]

The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs. [ABSTRACT FROM AUTHOR]

Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin's chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin's anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin's chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC. [ABSTRACT FROM AUTHOR]

Soil is a complex matrix where biotic and abiotic components establish a still unclear network involving bacteria, fungi, archaea, protists, protozoa, and roots that are in constant communication with each other. Understanding these interactions has recently focused on metagenomics, metatranscriptomics and less on metaproteomics studies. Metaproteomic allows total extraction of intracellular and extracellular proteins from soil samples, providing a complete picture of the physiological and functional state of the "soil community". The advancement of high-performance mass spectrometry technologies was more rapid than the development of ad hoc extraction techniques for soil proteins. The protein extraction from environmental samples is biased due to interfering substances and the lower amount of proteins in comparison to cell cultures. Soil sample preparation and extraction methodology are crucial steps to obtain high-quality resolution and yields of proteins. This review focuses on the several soil protein extraction protocols to date to highlight the methodological challenges and critical issues for the application of proteomics to soil samples. This review concludes that improvements in soil protein extraction, together with the employment of ad hoc metagenome database, may enhance the identification of proteins with low abundance or from non-dominant populations and increase our capacity to predict functional changes in soil. [ABSTRACT FROM AUTHOR]

Due to the spectacular number of studies focusing on epigenetics in the last few decades, and particularly for the last few years, the availability of a chronology of epigenetics appears essential. Indeed, our review places epigenetic events and the identification of the main epigenetic writers, readers and erasers on a historic scale. This review helps to understand the increasing knowledge in molecular and cellular biology, the development of new biochemical techniques and advances in epigenetics and, more importantly, the roles played by epigenetics in many physiological and pathological situations. [ABSTRACT FROM AUTHOR]

Many studies have provided evidence suggesting that caspases not only contribute to the neurodegeneration associated with Alzheimer's disease (AD) but also play essential roles in promoting the underlying pathology of this disease. Studies regarding the caspase inhibition draw researchers' attention through time due to its therapeutic value in the treatment of AD. In this work, we apply the "Movable Type" (MT) free energy method, a Monte Carlo sampling method extrapolating the binding free energy by simulating the partition functions for both free-state and bound-state protein and ligand configurations, to the caspase-inhibitor binding affinity study. Two test benchmarks are introduced to examine the robustness and sensitivity of the MT method concerning the caspase inhibition complexing. The first benchmark employs a large-scale test set including more than a hundred active inhibitors binding to caspase-3. The second benchmark includes several smaller test sets studying the relative binding free energy differences for minor structural changes at the caspase-inhibitor interaction interfaces. Calculation results show that the RMS errors for all test sets are below 1.5 kcal/mol compared to the experimental binding affinity values, demonstrating good performance in simulating the caspase-inhibitor complexing. For better understanding the protein-ligand interaction mechanism, we then take a closer look at the global minimum binding modes and free-state ligand conformations to study two pairs of caspase-inhibitor complexes with (1) different caspase targets binding to the same inhibitor, and (2) different polypeptide inhibitors targeting the same caspase target. By comparing the contact maps at the binding site of different complexes, we revealed how small structural changes affect the caspase-inhibitor interaction energies. Overall, this work provides a new free energy approach for studying the caspase inhibition, with structural insight revealed for both free-state and bound-state molecular configurations. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) in animal models induces cognitive deficits as well as the activation of caspase in the limbic system; both can be blocked by 2 weeks of treatment following MI using tricyclic antidepressants or selective serotonin uptake blockers. Here we used three different treatment schedules to test the short- and long-term effects of the combined serotonin-norepinephrine reuptake inhibitor desvenlafaxine on post-MI-associated cognitive deficits and caspase activation. MI was induced in 39 young adult rats, and 39 rats served as sham-operated controls. Desvenlafaxine (3 mg/kg/day, i.p.) or saline was administered according to one of three schedules: (1) for 2 weeks, starting right after surgery; (2) for 16 weeks, starting 2 weeks after surgery; (3) for 16 weeks, starting right after surgery. Behavior was tested 2 weeks (social interaction, passive avoidance) and 16 weeks (forced swimming, Morris water maze) after surgery. Caspase-3 and caspase-6 activities were measured 16 weeks after surgery. At 2 and 16 weeks post-surgery, saline-treated MI rats displayed performance deficits compared to desvenlafaxine-treated rats, regardless of the treatment schedule. Caspase-3 activity was higher in the amygdala (medial and lateral) and hippocampal CA3 region in untreated MI rats, whereas caspase-6 activity was higher in the CA1 region. Caspase-6 activity correlated positively with deficits in the Morris water maze. These results indicate that, independently of treatment schedules, various treatment schedules with desvenlafaxine can prevent MI-associated cognitive deficits and decrease caspase activities in the limbic system. [ABSTRACT FROM AUTHOR]

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a common disease that affects 3–5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6–8% of the population. Of great concern is that the number of cases of diabetes is constantly increasing, probably due to the increase in obesity and the sedentary nature of the population. According to the World Health Organization, in the year 2030 there will be 360 million people with diabetes, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on health systems that offer assistance to patients. In this review, we try to describe in an organized way the pathophysiological continuity between diabetes mellitus, endothelial dysfunction, and platelet hyperaggregation, highlighting the main molecular mechanisms involved and the interconnections. [ABSTRACT FROM AUTHOR]