Central Nervous Research Articles

A Comprehensive Review on Weight Gain following Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists for Obesity

Obesity is considered the leading public health problem in the medical sector. The phenotype includes overweight conditions that lead to several other comorbidities that drastically decrease health. Glucagon-like receptor agonists (GLP-1RAs) initially designed for treating type 2 diabetes mellitus (T2DM) had demonstrated weight loss benefits in several clinical trials. In vivo studies showed that GLP-1RA encourages reduced food consumption and consequent weight reduction by stimulating brown fat and enhancing energy outlay through the action of the sympathetic nervous system (SNS) pathways. Additionally, GLP-1RAs were found to regulate food intake through stimulation of sensory neurons in the vagus, interaction with the hypothalamus and hindbrain, and through inflammation and intestinal microbiota. However, the main concern with the use of GLP-1RA treatment was weight gain after withdrawal or discontinuation. We could identify three different ways that could lead to weight gain. Potential factors might include temporary hormonal adjustment in response to weight reduction, the central nervous system’s (CNS) incompetence in regulating weight augmentation owing to the lack of GLP-1RA, and β-cell malfunction due to sustained exposure to GLP-1RA. Here, we also review the data from clinical studies that reported withdrawal symptoms. Although the use of GLP-1RA could be beneficial in multiple ways, withdrawal after years has the symptoms reversed. Clinical studies should emphasize the downside of these views we highlighted, and mechanistic studies must be carried out for a better outcome with GLP-1RA from the laboratory to the bedside.

Rabies death in a prisoner: necessity for medical history documentation

Rabies is a zoonotic illness with a high mortality rate that attacks mammals' central nervous systems. It is a viral illness that may be avoided with immunization. Up to 99% of the human rabies transmissions occur in dogs, making them the primary cause of rabies mortality in humans. It is a case-report of rabies death in a 55-years old male, a prisoner from Phulbani Jail (Kandhamal), who was presented to MKCG Medical College and Hospital casualty with with chief complaints of difficulty in breathing and difficulty in drinking water since last night on 17 July 2023, at 11:19 pm. The patient had a history of dog bite exposure four years ago, for which he had not received any post-exposure prophylaxis. The patient was identified as having a likely case of rabies based on his previous history of animal bite and clinical manifestations. Patient was declared dead on 18 July 2023 at 10:30 am. Rabies diagnosis was confirmed by pathological examination of brain sample which showed presence of Negri bodies. This case-report focuses on the importance of proper medical history information including any animal bite exposure especially for convicts before admitting in prison so as to avoid later morbidity and its legal consequences. Such kind of incident also shows that there is lack of awareness regarding rabies in community. In this instance, mortality may have been prevented if the patient had finished the anti-rabies vaccine regimen and made it to a higher center in time for immunoglobulin. Increasing rabies vaccination awareness among the general public can help reduce rabies-related deaths.

Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.

Transient receptor potential canonical 3 (TRPC3) protein belongs to the TRP family of nonselective cation channels. Its activation occurs by signaling through a G protein-coupled receptor (GPCR) and a phospholipase C-dependent (PLC) pathway. Perturbations in the expression of TRPC3 are associated with a plethora of pathophysiological conditions responsible for disorders of the cardiovascular, immune, and central nervous systems. The recently solved cryo-EM structure of TRPC3 provides detailed inputs about the underlying mechanistic aspects of the channel, which in turn enables more efficient ways of designing small-molecule modulators. Pharmacologically targeting TRPC3 in animal models has demonstrated great efficacy in treating diseases including cancers, neurological disorders, and cardiovascular diseases. Despite extensive scientific evidence supporting some strong correlations between the expression and activity of TRPC3 and various pathophysiological conditions, therapeutic strategies based on its pharmacological modulations have not led to clinical trials. The development of small-molecule TRPC3 modulators with high safety, sufficient brain penetration, and acceptable drug-like profiles remains in progress. Determining the pathological mechanisms for TRPC3 involvement in human diseases and understanding the requirements for a drug-like TRPC3 modulator will be valuable in advancing small-molecule therapeutics to future clinical trials. In this review, we provide an overview of the origin and activation mechanism of TRPC3 channels, diseases associated with irregularities in their expression, and new development in small-molecule modulators as potential therapeutic interventions for treating TRPC3 channelopathies.

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

Copper Poisoning with Emphasis on Its Clinical Manifestations and Treatment of Intoxication

Background. Copper is an essential trace element found in the human body in an oxidized (Cu II) and reduced (Cu I) form. It plays a crucial role in the integrity and function of proteins and enzymes. Short-term and long-term exposure to copper can result in harmful effects and lead to clinical manifestations in multiple bodily systems, including the gastrointestinal tract, liver, kidneys, eyes, respiratory, cardiovascular, central nervous, endocrine, and hematopoietic systems. Objective. The purpose of this study is the importance of early recognition and diagnosis of copper poisoning immediate and necessary measures and the use of chelators. Materials and Methods. In this review article, authors from Pub Med, Scopus, and a toxicologic emergencies reference book from 1996 to 2024 are used. Result. An excessive increase in copper level produces reactive oxygen species that can cause lipid peroxidation in cell membranes, direct oxidation of proteins, and the breakdown of DNA and RNA molecules. All of these can generally be reasons for cell death. Conclusion. Assessing levels of copper in whole blood, free serum copper, 24-hr urine copper, liver biopsy for copper concentration, and ceruloplasmin play a crucial role in the diagnosis. The blood copper concentration is directly related to the severity of poisoning. Treatment for copper poisoning typically involves removing the source of exposure and administering medications to help remove the excess copper from the body. Supportive care for copper intoxication usually includes managing vomiting, correcting fluids and electrolytes, and stabilizing vital signs. Chelators like D-penicillamine, succimer, trientine, tetrathiomolybdate, and PBT-2 have been utilized in treatment.

Infrared Neuromodulation - a Review.

Infrared (IR) neuromodulation (INM) is an emerging light-based neuromodulation approach that can reversibly control neuronal and muscular activities through the transient and localized deposition of pulsed IR light without requiring any chemical or genetic pre-treatment of the target cells. Though the efficacy and short-term safety of INM have been widely demonstrated in both peripheral and central nervous systems, the investigations of the detailed cellular and biological processes and the underlying biophysical mechanisms are still ongoing. In this review, we discuss the current research progress in the INM field with a focus on the more recently discovered IR nerve inhibition (INI). Major biophysical mechanisms associated with IR nerve stimulation (INS) are summarized. As the INM effects are primarily attributed to the spatiotemporal thermal transients induced by water and tissue absorption of pulsed IR light, temperature monitoring techniques and simulation models adopted in INM studies are discussed. Potential translational applications, current limitations, and challenges of the field will be elucidated to provide guidance for future INM research and advancement.&#xD.

Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents.

Neurodegeneration is a gradual decay process leading to the depletion of neurons in both the central and peripheral nervous systems, ultimately resulting in cognitive dysfunctions and the deterioration of brain functions, alongside a decline in motor skills and behavioral capabilities. Neurodegenerative disorders (NDs) impose a substantial socio-economic strain on society, aggravated by the advancing age of the world population and the absence of effective remedies, predicting a negative future. In this context, the urgency of discovering viable therapies is critical and, despite significant efforts by medicinal chemists in developing potential drug candidates and exploring various small molecules as therapeutics, regrettably, a truly effective treatment is yet to be found. Nitrogen heterocyclic compounds, and particularly those containing the indole nucleus, which has emerged as privileged scaffold, have attracted particular attention for a variety of pharmacological applications. This review analyzes the rational design strategy adopted by different research groups for the development of anti-neurodegenerative indole-based compounds which have the potential to modulate various molecular targets involved in NDs, with reference to the most recent advances between 2018 and 2023.

Capitella teleta gets left out: possible evolutionary shift causes loss of left tissues rather than increased neural tissue from dominant-negative BMPR1

BackgroundThe evolution of central nervous systems (CNSs) is a fascinating and complex topic; further work is needed to understand the genetic and developmental homology between organisms with a CNS. Research into a limited number of species suggests that CNSs may be homologous across Bilateria. This hypothesis is based in part on similar functions of BMP signaling in establishing fates along the dorsal-ventral (D-V) axis, including limiting neural specification to one ectodermal region. From an evolutionary-developmental perspective, the best way to understand a system is to explore it in a wide range of organisms to create a full picture.MethodsHere, we expand our understanding of BMP signaling in Spiralia, the third major clade of bilaterians, by examining phenotypes after expression of a dominant-negative BMP Receptor 1 and after knock-down of the putative BMP antagonist Chordin-like using CRISPR/Cas9 gene editing in the annelid Capitella teleta (Pleistoannelida).ResultsEctopic expression of the dominant-negative Ct-BMPR1 did not increase CNS tissue or alter overall D-V axis formation in the trunk. Instead, we observed a unique asymmetrical phenotype: a distinct loss of left tissues, including the left eye, brain, foregut, and trunk mesoderm. Adding ectopic BMP4 early during cleavage stages reversed the dominant-negative Ct-BMPR1 phenotype, leading to a similar loss or reduction of right tissues instead. Surprisingly, a similar asymmetrical loss of left tissues was evident from CRISPR knock-down of Ct-Chordin-like but concentrated in the trunk rather than the episphere.ConclusionsOur data highlight a novel asymmetrical phenotype, giving us further insight into the complicated story of BMP’s developmental role. We further solidify the hypothesis that the function of BMP signaling during the establishment of the D-V axis and CNS is fundamentally different in at least Pleistoannelida, possibly in Spiralia, and is not required for nervous system delimitation in this group.

Division of labor for defensive retaliation and preemption by the peripheral and central nervous systems in the nudibranch Berghia.

Relatively little is known about how peripheral nervous systems (PNSs) contribute to the patterning of behavior in which their role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch Berghia stephanieae, which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle. Our investigations revealed that bristling constitutes a stereotyped but non-reflexive two-stage behavior: an initial adduction of proximate cerata to sting the offending stimulus (stage 1) followed by a coordinated radial extension of remaining cerata to create a pincushion-like defensive screen around the animal (stage 2). In decerebrated specimens, stage 1 bristling was preserved, while stage 2 bristling was replaced by slower, uncoordinated ceratal movements. We conclude from these observations that, first, the animal's PNS and central nervous system (CNS) mediate stages 1 and 2 of bristling, respectively; second, the behavior propagates through the body utilizing both peripheral- and central-origin nerve networks that support different signaling kinetics; and third, the former network inhibits the latter in the body region being stimulated. These findings extend our understanding of the PNS' computational capacity and provide insight into a neuroethological scheme in which the CNS and PNS both independently and interactively pattern different aspects of non-reflexive behavior.

RASopathies for Radiologists.

RASopathies are a heterogeneous group of genetic syndromes caused by germline mutations in a group of genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include neurofibromatosis type 1, Legius syndrome, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, central conducting lymphatic anomaly, and capillary malformation-arteriovenous malformation syndrome. These disorders are grouped together as RASopathies based on our current understanding of the Ras/MAPK pathway. Abnormal activation of the Ras/MAPK pathway plays a major role in development of RASopathies. The individual disorders of RASopathies are rare, but collectively they are the most common genetic condition (one in 1000 newborns). Activation or dysregulation of the common Ras/MAPK pathway gives rise to overlapping clinical features of RASopathies, involving the cardiovascular, lymphatic, musculoskeletal, cutaneous, and central nervous systems. At the same time, there is much phenotypic variability in this group of disorders. Benign and malignant tumors are associated with certain disorders. Recently, many institutions have established multidisciplinary RASopathy clinics to address unique therapeutic challenges for patients with RASopathies. Medications developed for Ras/MAPK pathway-related cancer treatment may also control the clinical symptoms due to an abnormal Ras/MAPK pathway in RASopathies. Therefore, radiologists need to be aware of the concept of RASopathies to participate in multidisciplinary care. As with the clinical manifestations, imaging features of RASopathies are overlapping and at the same time diverse. As an introduction to the concept of RASopathies, the authors present major representative RASopathies, with emphasis on their imaging similarities and differences. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Effects of 90 dB pure tone exposure on auditory and cardio-cerebral system functions in macaque monkeys

Excessive noise exposure can pose significant health risks to humans. In addition to causing direct damage to the auditory system, noise exposure is also associated with pathological changes or injuries in the cardiovascular and central nervous systems. Uncovering the physiological effects of noise exposure on the body contributes to a better understanding of the potential health risks associated with noise exposure, aiding in the establishment and updating of safety standards and limits for occupational noise exposure. This study focused on three male macaque monkeys as subjects. Low-intensity pure tone exposure (intensity: 90 dB, frequency: 500 Hz, repetition rate: 40 Hz, 10 min per day, continuously exposed for 5 days) was administered. Evaluations were conducted before noise exposure, immediately after exposure, and at 7, 14, and 28 days post-exposure. Auditory brainstem response (ABR) tests were conducted to assess the impact of noise exposure on the hearing of the macaque monkeys. Electrocardiograms (ECG) were performed to evaluate changes in the heart function of the monkeys after noise exposure. Electroencephalograms (EEG) were recorded to assess noise-induced changes in brain function. The results of the study revealed that, compared to pre-exposure levels, the average threshold for the V wave of the right ear of the Macaque monkeys increased by approximately 30 dB immediately after exposure (p < 0.01), and it returned to normal within 7 days. The ECG results indicated that one of the macaque monkeys exhibited an RS-type QRS wave, and inverted T waves from immediately after exposure to 14 days, which normalized at 28 days. The other two macaque monkeys showed no significant changes in their ECG parameters. Changes in EEG parameters demonstrated that main brain regions exhibited significant activation at 40 Hz during noise exposure. Noise stimulation with a 40 Hz repetition rate induced abnormal resting-state electroencephalogram power spectral density (PSD) across the δ (1–3 Hz), θ (4–8 Hz), α (8–12 Hz), β1 (12–20 Hz), β2 (20–30 Hz), and γ (30–48 Hz) frequency bands. After noise exposure, the PSD in main brain regions, particularly those represented by the temporal lobe, exhibited a decreasing trend across all frequency bands, with no clear recovery over time. In summary, exposure to 90 dB pure tone resulted in transient hearing threshold shifts, inverted T waves, activation of brain regions at 40 Hz, and disrupted PSD of resting-state EEG in macaque monkeys. While these effects were observed, they exhibited individual differences. This study investigated the physiological changes in auditory and cardio-cerebral systems in macaque monkeys following low-intensity noise exposure, which could be informative for noise protection and the establishment of safety standards for human. However, the exact mechanisms involved require further pathological and behavioral exploration.

Exercise Physiology: A Review of Established Concepts and Current Questions

Exercise physiology is the science that studies the processes of physical activity and their impact on the body. It usually requires a multidisciplinary approach with a team of experts because of the multiple physiological systems involved. At the cellular level, exercise can trigger a cascade of events that involve metabolic pathways, muscle recruitment and conditioning, neuromuscular adaptations, and optimization of energy production. On a systematic level, this has involved the cardiovascular system, the respiratory system, the musculoskeletal system, the peripheral and central nervous systems, and even the endocrine system to improve adaptation to meet the demands of exercise, improving strength and endurance with the goal of maximizing performance. This field, which began largely with a focus on the kinetics of oxygen consumption and the relationship between aerobic and anaerobic metabolism, has expanded with technological advancements such as wearable devices, advanced imaging techniques, and genomics, which has allowed for a greater appreciation of the physiologic responses of exercise at the level of molecular and cellular interactions. Recently, this science has evolved into the study of overall health promotion and disease prevention to meet individual fitness needs and goals. This philosophy, which is captured by the motto “Exercise is Medicine”, has been adopted as a Global Health Initiative by the World Health Organization (WHO). Despite the advancements in technology and impactful, large-scale studies, a variety of questions, such as how physical activity interacts with aging to affect physical and cognitive function, how inactivity influences acute and chronic disease states, and how we maximize human performance in extreme conditions like microgravity environments, remain. The purpose of this review is to present and discuss established concepts, controversial topics, and unanswered questions within exercise physiology that have allowed this field to become a science that embraces the overall well-being of individuals.

Analgesic candidate adenosine A3 receptors are expressed by perineuronal peripheral macrophages in human dorsal root ganglion and spinal cord microglia.

Adenosine receptors are a family of purinergic G protein-coupled receptors that are widely distributed in bodily organs and in the peripheral and central nervous systems. Recently, antihyperalgesic actions have been suggested for the adenosine A3 receptor, and its agonists have been proposed as new neuropathic pain treatments. We hypothesized that these receptors may be expressed in nociceptive primary afferent neurons. However, RNA sequencing across species, eg, rat, mouse, dog, and human, suggests that dorsal root ganglion (DRG) expression of ADORA3 is inconsistent. In rat and mouse, Adora3 shows very weak to no expression in DRG, whereas it is well expressed in human DRG. However, the cell types in human DRG that express ADORA3 have not been delineated. An examination of DRG cell types using in situ hybridization clearly detected ADORA3 transcripts in peripheral macrophages that are in close apposition to the neuronal perikarya but not in peripheral sensory neurons. By contrast, ADORA1 was found primarily in neurons, where it is broadly expressed at low levels. These results suggest that a more complex or indirect mechanism involving modulation of macrophage and/or microglial cells may underlie the potential analgesic action of adenosine A3 receptor agonism.

A simple and highly sensitive flexible sensor with extended-gate field-effect transistor for epinephrine detection utilizing InZnSnO sensing films

This study introduces a straightforward method for depositing InZnSnO films onto flexible polyimide substrates at room temperature, enabling their application in electrochemical pH sensing and the detection of epinephrine. A comprehensive analysis of these sensing films, spanning structural, morphological, compositional, and profiling characteristics, was conducted using diverse techniques, including X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy. The investigation into the influence of oxygen flow rates on the performance of InZnSnO sensitive films revealed a significant correlation between their structural properties and sensing capabilities. Notably, exposure to an oxygen flow rate of 30/2 (Ar/O2) the ratio of resulted in the InZnSnO sensitive film demonstrating outstanding pH sensitivity at 59.58 mV/pH within a broad pH range of 2–12, surpassing the performance observed with other oxygen flow rates. Moreover, under this specific condition, the film exhibited excellent stability, with a minimal drift rate of 0.14 mV/h at pH 7 and a low hysteresis voltage of 1.8 mV during a pH cycle of 7 → 4→7 → 10→7. Given the critical role of epinephrine in mammalian central nervous and hormone systems, monitoring its levels is essential for assessing human health. To facilitate the detection of epinephrine, we utilized the carboxyl group of 4-formylphenylboronic acid to enable a reaction with the amino group of the 3-aminopropyltriethoxysilane-coated InZnSnO film. Through optimization, the resulting InZnSnO-based flexible sensor displayed a broad and well-defined linear relationship within the concentration range of 10−7 to 0.1 μM. In practical applications, this sensor proved effective in analyzing epinephrine in human serum, showcasing notable selectivity, stability, and reproducibility. The promising outcomes of this study underscore the potential for future applications, leveraging the advantages of electrochemical sensors, including affordability, rapid response, and user-friendly operation.

Augmenting locomotor perception by remapping tactile foot sensation to the back

BackgroundSensory reafferents are crucial to correct our posture and movements, both reflexively and in a cognitively driven manner. They are also integral to developing and maintaining a sense of agency for our actions. In cases of compromised reafferents, such as for persons with amputated or congenitally missing limbs, or diseases of the peripheral and central nervous systems, augmented sensory feedback therefore has the potential for a strong, neurorehabilitative impact. We here developed an untethered vibrotactile garment that provides walking-related sensory feedback remapped non-invasively to the wearer’s back. Using the so-called FeetBack system, we investigated if healthy individuals perceive synchronous remapped feedback as corresponding to their own movement (motor awareness) and how temporal delays in tactile locomotor feedback affect both motor awareness and walking characteristics (adaptation).MethodsWe designed the system to remap somatosensory information from the foot-soles of healthy participants (N = 29), using vibrotactile apparent movement, to two linear arrays of vibrators mounted ipsilaterally on the back. This mimics the translation of the centre-of-mass over each foot during stance-phase. The intervention included trials with real-time or delayed feedback, resulting in a total of 120 trials and approximately 750 step-cycles, i.e. 1500 steps, per participant. Based on previous work, experimental delays ranged from 0ms to 1500ms to include up to a full step-cycle (baseline stride-time: µ = 1144 ± 9ms, range 986-1379ms). After each trial participants were asked to report their motor awareness.ResultsParticipants reported high correspondence between their movement and the remapped feedback for real-time trials (85 ± 3%, µ ± σ), and lowest correspondence for trials with left-right reversed feedback (22 ± 6% at 600ms delay). Participants further reported high correspondence of trials delayed by a full gait-cycle (78 ± 4% at 1200ms delay), such that the modulation of motor awareness is best expressed as a sinusoidal relationship reflecting the phase-shifts between actual and remapped tactile feedback (cos model: 38% reduction of residual sum of squares (RSS) compared to linear fit, p < 0.001). The temporal delay systematically but only moderately modulated participant stride-time in a sinusoidal fashion (3% reduction of RSS compared a linear fit, p < 0.01).ConclusionsWe here demonstrate that lateralized, remapped haptic feedback modulates motor awareness in a systematic, gait-cycle dependent manner. Based on this approach, the FeetBack system was used to provide augmented sensory information pertinent to the user’s on-going movement such that they reported high motor awareness for (re)synchronized feedback of their movements. While motor adaptation was limited in the current cohort of healthy participants, the next step will be to evaluate if individuals with a compromised peripheral nervous system, as well as those with conditions of the central nervous system such as Parkinson’s Disease, may benefit from the FeetBack system, both for maintaining a sense of agency over their movements as well as for systematic gait-adaptation in response to the remapped, self-paced, rhythmic feedback.

The pattern of neurological disorders requiring hospitalization during the COVID-19 era: an experience from Fayoum University Hospital, Egypt

BackgroundCoronavirus was primarily discovered in December 2019, causing pneumonia and severe acute respiratory syndrome. It was reported several neurological symptoms associated with COVID-19. Both the central and peripheral nervous systems could be affected which might result in a higher mortality rate in hospitalized patients. This study aimed to determine the spectrum of neurological clinical presentations among patients admitted to Fayoum University Hospital before, during, and after the COVID-19 era and to examine the influence of COVID-19 vaccines mandated by the Egyptian government on neurological disorders.MethodsThis is a historical cohort study that was conducted on patients admitted to the Neurology Department at Fayoum University Hospital before, during, and after COVID-19 outbreaks from January 1st, 2018, to July 31, 2022. All participants had undergone thorough history taking and neurological examination and the necessary investigations according to the suspected diagnosis. All hospitalized patients during the COVID-19 pandemic were positive for the virus, as determined by either a positive rapid antigen test or a positive real-time reverse transcription polymerase chain reaction (RT-PCR).ResultsIt was shown that the patients hospitalized during the COVID-19 era were notably older, smokers, and diabetic in comparison to other groups. Cerebrovascular disorders were more prevalent in the COVID-19 pandemic. Surprisingly, compared to prior times, individuals with autoimmune-mediated neurological diseases had higher hospitalization rates than those with other neurological disorders. Patients who were not vaccinated reported more vascular complications than those who got them. However, patients who received vaccination exhibited significantly higher neurological complications as regards, exacerbation of paroxysmal disorders.ConclusionIt was concluded that the frequency of hospitalizations with cerebrovascular disorders and autoimmune-mediated illnesses was significantly influenced during the pandemic era. Although COVID-19 vaccinations have potential adverse effects, they have played a crucial role in preventing serious neurological problems.

Modeling ferroptosis in human dopaminergic neurons: Pitfalls and opportunities for neurodegeneration research

The activation of ferroptosis is being pursued in cancer research as a strategy to target apoptosis-resistant cells. By contrast, in various diseases that affect the cardiovascular system, kidneys, liver, and central and peripheral nervous systems, attention is directed toward interventions that prevent ferroptotic cell death. Mechanistic insights into both research areas stem largely from studies using cellular in vitro models. However, intervention strategies that show promise in cellular test systems often fail in clinical trials, which raises concerns regarding the predictive validity of the utilized in vitro models.In this study, the human LUHMES cell line, which serves as a model for human dopaminergic neurons, was used to characterize factors influencing the activation of ferroptosis. Erastin and RSL-3 induced cell death that was distinct from apoptosis. Parameters such as the differentiation state of LUHMES cells, cell density, and the number and timing of medium changes were identified as determinants of sensitivity to ferroptosis activation. In differentiated LUHMES cells, interventions at mechanistically divergent sites (iron chelation, coenzyme Q10, peroxidase mimics, or inhibition of 12/15-lipoxygenase) provide almost complete protection from ferroptosis. LUHMES cells allowed the experimental modulation of intracellular iron concentrations and demonstrated a correlation between intracellular iron levels, the rate of lipid peroxidation, as well as the sensitivity of the cells to ferroptotic cell death.These findings underscore the importance of understanding the various factors that influence ferroptosis activation and highlight the need for well-characterized in vitro models to enhance the reliability and predictive value of observations in ferroptosis research, particularly when translating findings into in vivo contexts.

Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System.

Implantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long-term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed-loop control algorithms to successfully realize this approach are highlighted. It is believed that these new "organ neuroprostheses" are going to become more and more valuable and very effective solutions in the years to come.

Effect of Dietary Eicosapentaenoic and Docosahexaenoic Fatty Acid Supplementation during the Last Month of Gestation on Fatty Acid Metabolism and Oxidative Status in Charolais Cows and Calves.

Fatty acids (FAs) are of utmost importance in the peripartal period for the development of the central nervous and immune systems of the newborn. The transport of polyunsaturated fatty acids (PUFAs) through the placenta is considered to be minimal in ruminants. Nevertheless, the cow's FAs are the main source of FAs for the calf during gestation. This research aimed to investigate the influence of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation during late gestation on the FA metabolism of cows and their calves. A total of 20 Charolais cows during the last month of their gestation were included in the feeding trial and were divided into a control group (CON) and an experimental group (EPA + DHA). The latter received a supplement in the amount of 100 g/day (9.1 and 7.8 g/cow/day of EPA and DHA, respectively). Supplementation of low-dose EPA and DHA alters colostrum and milk fatty acid composition through the elevation of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) without affecting milk fat and protein concentrations and oxidative status. Plasma composition in cows was significantly altered, while the same effect was not detected in calf plasma. No significant change in mRNA expression was detected for the genes fatty acid synthase (FASN) and acetyl-CoA carboxylase alpha (ACACA).

The bacterial microbiota of the gastrointestinal tract of dairy cattle: structure, functions, importance (review)

The review presents the generalized material of experimental studies and review works (114 sources, including 110 foreign) on studying the composition of bacterial microbiota of the gastrointestinal tract in cattle depending on age, clinical condition of animals and level of productivity, shows the influence of the functional activity of microbiota on the formation and development of the organism. The microbiota affects the health and productive qualities of dairy cattle. The bacterial community of the gastrointestinal tract plays a crucial role in the digestive system. This complex system with feedback, where on the one hand, the microbiota is influenced by the genotype of the host, feed base, living conditions, breeding methods, and drugs used, and on the other hand, the microbiota primarily affects plastic and energy metabolism, but also indirectly affects respiratory, urinary, central nervous, and immune systems of the body. Bacterial diversity is laid down during the fetal period, undergoes significant changes during calf growth, and remains stable throughout life, adapting to changing conditions. Modern studies of gastrointestinal diseases are increasingly focusing on the composition of the microbial community, pointing to the dangers of antibiotic use and the need for a transition to probiotic and prebiotic therapy. Productive qualities of cows, such as milk yield and fat and protein content, also depend on the composition of the microbiota.