Modulation Of System Research Articles

Nasal lymphatic obstruction of CSF drainage as a possible cause of Alzheimer's disease and dementia.

Alzheimer's disease, the most common form of dementia among older adults, slowly destroys memory and thinking skills. In recent years, scientists have made tremendous progress in understanding Alzheimer's disease, still, they do not yet fully understand what causes the disease. This article proposes a novel etiology for Alzheimer's disease. Our hypothesis developed from a review of nuclear medicine scans, in which the authors observed a significant increase in nasal turbinate vasodilation and blood pooling in patients with hypertension, sleep apnea, diabetes and/or obesity, all risk factors for Alzheimer's disease. The authors propose that nasal turbinate vasodilation and resultant blood pooling lead to the obstruction of normal nasal lymphatic clearance of cerebrospinal fluid and its waste products from the brain. The nasal turbinate vasodilation, due to increased parasympathetic activity, occurs alongside the well-established increased sympathetic activity of the cardiovascular system as seen in patients with hypertension. The increased parasympathetic activity is likely due to an autonomic imbalance secondary to the increase in worldwide consumption of highly processed food associated with dysregulation of the glucose regulatory system. The authors' hypothesis offers a novel mechanism and a new paradigm for the etiology of Alzheimer's disease and helps explain the rapid worldwide rise in the disease and other dementias which are expected to double in the next 20 years. This new paradigm provides compelling evidence for the modulation of the parasympathetic nervous system as a novel treatment strategy for Alzheimer's disease and other degenerative brain diseases, specifically targeting nasal turbinate lymphatic flow.

Nitric Oxide-Dependent Regulation of Oxygen-Related Processes in a Rat Model of Lead Neurotoxicity: Influence of the Hypoxia Resistance Factor

Background/Aims: Lead exposure is known to induce oxidative stress and neurotoxicity. Nitric oxide (NO) plays an important role in modulating oxidative stress, with L-arginine as a precursor of NO and Nω-nitro-L-arginine (L-NNA) as an inhibitor of NO synthase, an enzyme that catalyses the production of nitric oxide (NO) from L-arginine. Methods: This study investigated the differential effects of L-arginine and L-NNA on markers of oxidative stress and biochemical changes in brain tissue from rats with different levels of resistance to hypoxia exposed to lead nitrate. Rats with either low or high resistance to hypoxia were exposed to lead nitrate (oral 3.6 mg lead nitrate/kg b.w. per day for 30 days) and treated with L-arginine (600 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate) or L-NNA (35 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate). Brain tissue samples were analysed for lipid peroxidation, oxidative modification of proteins, and activity of antioxidant enzymes, including superoxide dismutase, catalase, glutathione reductase, and peroxidase, and total antioxidant status (TAS). We also examined the biomarkers of biochemical pathways involving the activity of alanine and aspartate aminotransferases, succinate dehydrogenase (SDH), and α-ketoglutarate dehydrogenase (KGDH). In addition, the trend observed was supported by assessments of the acetylcholine levels and acetylcholinesterase activity (ACh-AChE system) in brain tissue. Results: In rats with low resistance to hypoxia, the L-arginine treatment significantly reduced lipid peroxidation and oxidative protein modification but increased antioxidant enzyme activity, suggesting a protective effect against lead-induced oxidative stress. Conversely, in rats with high resistance to hypoxia, L-NNA had a protective effect, reducing lead-induced oxidative damage and decreasing lipid peroxidation, whereas L-arginine exacerbated oxidative stress and impaired antioxidant defences. These findings were supported by corresponding changes in the acetylcholine-acetylcholinesterase system, reflecting the observed patterns of lead-induced oxidative stress and neurotoxicity. The study shows that L-arginine exerts a protective effect by reducing lead-induced oxidative damage via an improvement in TAS. Our study shows that lead nitrate exposure significantly increases ala-nine and aspartate aminotransferase activity in brain tissue, with L-arginine exacerbating and L-NNA reversing this effect. The lead nitrate exposure also affected the activities of SDH and KGDH, which are important for cellular energy production and hypoxia resistance, with L-arginine altering SDH activity depending on the level of resistance and L-NNA enhancing both SDH and KGDH activities. These trends were further validated by alterations in the ACh-AChE system, highlighting the differential role of NO-dependent mechanisms in modulating lead-induced neurotoxicity based on hypoxia resistance. Conclusion: These findings suggest potential targeted therapeutic strategies based on the oxidative stress profile and highlight the potential of nitric oxide system modulators in counteracting lead-induced biochemical alterations and the dynamics of the ACh-AChE system depending on the individual physiological reactivity of organisms.

Organic matter-induced physiological responses and modulation of the enzymatic system in Sorghum bicolor (L) Moench genotypes cultivated in saline soil

Sorghum bicolor (L.) Moench is a crop with numerous applications that serves as a food source for humans and animals. However, soils with high salt concentrations compromise the initial development of the crop, and the addition of organic matter can mitigate the damage caused by salinity. The present study aimed to verify the effect of organic matter on salinity on the physiology and enzymatic profiles of two sorghum varieties, BRS Ponta Negra and BRS 373. The experiment was conducted in a completely randomized design (DIC) in a 4 x 4 x 2 arrangement, using different doses of organic matter as recommended (100%, 200%, 300%, and 400%) and the two sorghum varieties, with 4 replications. The variables analysed were: photosynthetic rate (A), transpiration (E), stomatal conductance (Gs), and enzymatic activity of ascorbate peroxidase (APX), polyphenoloxidase (POL), and catalase (CAT). The results showed that the A, E, and Gs responded differently to different doses of organic matter (OM); these responses were influenced by the isolated effects of the varieties or doses of organic matter, and their behaviour differed between the two analysed varieties. The A, E, and Gs showed contrasting response patterns between different doses of OM in variety 1 (BRS Ponta Negra) and variety 2 (BRS 373). These responses were influenced by the isolated effects of the varieties and/or doses of organic matter, showing different behaviours among the tested varieties.

Exploring potential working mechanisms of accelerated HF-rTMS in refractory major depression with a focus on locus coeruleus connectivity.

This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD). We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain's noradrenergic system and key to mood regulation and stress response. A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement. We observed such LC functional connectivity decreases with several brain regions, including the superior frontal gyrus, precentral gyrus, middle occipital gyrus, and cerebellum. Moreover, our exploratory analyses hint at a possible role for E-field modeling in forecasting clinical outcomes. Additional analyses suggest potential genetic and dopaminergic factors influencing changes in LC functional connectivity in relation to clinical response. The findings of this study underscore the pivotal role of the LC in orchestrating higher cognitive functions through its extensive connections with the prefrontal cortices, facilitating decision-making, influencing attention, and addressing depressive rumination. Additionally, the observed enhancement in LC-(posterior) cerebellar connectivity not only highlights the cerebellum's role in moderating clinical outcomes through noradrenergic system modulation but also suggests its potential as a predictive marker for aHF-rTMS efficacy. These results reveal new insights into the neural mechanisms of refractory depression and suggest therapeutic targets for enhancing noradrenergic activity, thereby addressing both cognitive and psychomotor symptoms associated with the disorder.

Short-Period Skyrmion Crystals in Itinerant Body-Centered Tetragonal Magnets

In this study, we investigate the stability of a magnetic skyrmion crystal with short-period magnetic modulations in a centrosymmetric body-centered tetragonal system. By performing the simulated annealing for the spin model, incorporating the effects of the biquadratic interaction and high-harmonic wave–vector interaction in momentum space, we find that the double-Q square skyrmion crystal consisting of two spin density waves is stabilized in an external magnetic field. We also show that double-Q states appear in both low- and high-field regions; the low-field spin configuration is characterized by an anisotropic double-Q modulation consisting of a superposition of the spiral wave and sinusoidal wave, while the high-field spin configuration is characterized by an isotropic double-Q modulation consisting of a superposition of two sinusoidal waves. Furthermore, we show that the obtained multiple-Q instabilities can be realized for various ordering wave vectors. The results provide the possibility of realizing the short-period skyrmion crystals under the body-centered tetragonal lattice structure.

Flavonoids against depression: a comprehensive review of literature.

Depression is a state of low mood and aversion to activity, which affects a person's thoughts, behavior, motivation, feelings, and sense of wellbeing. Pharmacologic therapies are still the best effective treatment of depression. Still, most antidepressant drugs have low efficacy and delayed onset of therapeutic action, have different side effects, and even exacerbate depression. Such conditions make it possible to look for alternatives. Consequently, we decided to summarize the impact of flavonoids on depression in this review. We searched scientific databases such as SCOPUS, PubMed, and Google Scholar to find relevant studies until July 2022. A wide variety of natural components have been shown to alleviate depression, one of which is flavonoids. Due to the growing tendency to use natural antidepressant drugs, scientific studies are increasingly being conducted on flavonoids. This study aims to review the latest scientific researches that indicate the antidepressant potential of flavonoids. Various mechanisms include neurotransmitter system modulation and dopaminergic, noradrenergic, and serotonergic pathways regulation in the central nervous system. Different compounds of flavonoids have antidepressant properties in vivo or in vitro experiments or clinical trials and can be used as alternative and complementary treatments for depression. In general, it was observed that there were no severe side effects. Our study proves the antidepressant potential of flavonoids, and considering the limited side effects, they can be used as complementary medicine for depressed patients.

Exaggerated postnatal surge of orexin neurons and the effects of elimination of excess orexin on blood pressure and exaggerated chemoreflex in spontaneously hypertensive rats.

An overactive orexin (OX) system is associated with neurogenic hypertension and an exaggerated chemoreflex in spontaneously hypertensive rats (SHRs). However, the chronology and mechanism of this association is unclear. We hypothesized that increased postnatal neurogenesis of OX neurons in SHRs precedes and contributes to the aberrant increase in mean arterial blood pressure (MAP) and the exaggerated response to hypercapnia during postnatal development. Using immunohistochemical methods and bromodeoxyuridine, we mapped the timeline of orexin neuron neurogenesis and maturation during early postnatal development. We then used whole-body plethysmography with EEG and EMG to map the development of mean arterial pressure (MAP) and state regulation. Finally, we used OX-targeted saporin toxin to determine the effects of eliminating excess OX neurons on the elevated MAP and exaggerated chemoreflex in adult SHRs. We found that both SHRs and Wistar-Kyoto (WKY) rats experienced postnatal increases in OX neurons. However, SHRs experienced a greater increase than WKY rats before P15, which led to significantly more OX neurons in SHRs than age-matched WKY controls by P15-16 (3,720 ± 780 vs. 2,406 ± 363, p = 0.005). We found that neurogenesis, as evidenced by BrdU staining in OX-positive neurons, was the primary contributor to the excess OX neurons in SHRs during early postnatal development. While SHRs develop more OX neurons by P15-16, SHRs and normotensive WKY control rats have similar MAP during postnatal development until P25 in wakefulness (81.6 ± 6.6 vs. 67.5 ± 6.8mmHg, p = 0.006) and sleep (79.3 ± 6.1 vs. 66.6 ± 6.5, p = 0.009), about 10 days after the surge of OX neurons. By selectively eliminating excess (∼30%) OX neurons in SHRs, we saw a significantly lowered MAP and hypercapnic ventilatory chemoreflex compared to non-lesioned SHRs at P40. Additionally, we found unique signatures in state indicative of the attention defecit phenotype commonly associated with this model. We suggest that the postnatal increase of OX neurons, primarily attributed to exaggerated postnatal OX neurogenesis, may be necessary for the development of higher MAP and exaggerated chemoreflex in SHRs, and modulation of the overactive OX system may have a potential therapeutic effect during the pre-hypertensive period.

Mind the GAPS: Glia associated with psychological stress.

Glial cells are an integral component of the nervous system, performing crucial functions that extend beyond structural support, including modulation of the immune system, tissue repair, and maintaining tissue homeostasis. Recent studies have highlighted the importance of glial cells as key mediators of stress responses across different organs. This review focuses on the roles of glial cells in peripheral tissues in health and their involvement in diseases linked to psychological stress. Populations of glia associated with psychological stress ("GAPS") emerge as a promising target cell population in our basic understanding of stress-associated pathologies, highlighting their role as mediators of the deleterious effects of psychological stress on various health conditions. Ultimately, new insights into the impact of stress on glial cell populations in the periphery may support clinical efforts aimed at improving the psychological state of patients for improved health outcomes.

Probiotic interventions and quality of life in patients with gastrointestinal diseases: A comprehensive review.

Gastrointestinal disorders manifest through disruptions in gastrointestinal functionality accompanied by dysbiosis within the microbiome. Probiotics are considered biological agents with potential therapeutic efficacy in managing gastrointestinal pathologies by modulating the gut microbiota. Nevertheless, several hurdles, such as safety considerations, resilience to stressors, post-colonization quantifications, and evaluative modalities, may impede the adoption of probiotics for gastrointestinal disorders. Herein, we performed online research using 6 databases: Scopus, ScienceDirect, PubMed, Web of Science, Cochrane Library, and Ovid. Inclusion criteria were mostly articles published in the years 2015-2024, concerning the association between probiotics and gastrointestinal diseases. This review aimed to provide comprehensive data regarding the latest studies in this area. Additionally, this review delineates the various aspects of probiotic use, including both the positive and negative aspects, as well as the role of probiotics in immune system modulation and the prevention of various diseases. Also, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics in the management of COVID-19. Given the extensive adoption of probiotic formulations as microecological interventions for gastrointestinal disorders, a comprehensive understanding of the challenges inherent in their application and the implementation of contemporary methodologies to enhance probiotic colonization and evaluation systems are paramount for harnessing probiotics as viable biotherapeutic agents. However, there is a need for additional studies to confirm the potential role of probiotics as a suitable target in the treatment of gastrointestinal diseases.

Elevated serum mtDNA in COVID-19 patients is linked to SARS-CoV-2 envelope protein targeting mitochondrial VDAC1, inducing apoptosis and mtDNA release

Mitochondria dysfunction is implicated in cell death, inflammation, and autoimmunity. During viral infections, some viruses employ different strategies to disrupt mitochondria-dependent apoptosis, while others, including SARS-CoV-2, induce host cell apoptosis to facilitate replication and immune system modulation. Given mitochondrial DNAs (mtDNA) role as a pro-inflammatory damage-associated molecular pattern in inflammatory diseases, we examined its levels in the serum of COVID-19 patients and found it to be high relative to levels in healthy donors. Furthermore, comparison of serum protein profiles between healthy individuals and SARS-CoV-2-infected patients revealed unique bands in the COVID-19 patients. Using mass spectroscopy, we identified over 15 proteins, whose levels in the serum of COVID-19 patients were 4- to 780-fold higher. As mtDNA release from the mitochondria is mediated by the oligomeric form of the mitochondrial-gatekeeper—the voltage-dependent anion-selective channel 1 (VDAC1)—we investigated whether SARS-CoV-2 protein alters VDAC1 expression. Among the three selected SARS-CoV-2 proteins, small envelope (E), nucleocapsid (N), and accessory 3b proteins, the E-protein induced VDAC1 overexpression, VDAC1 oligomerization, cell death, and mtDNA release. Additionally, this protein led to mitochondrial dysfunction, as evidenced by increased mitochondrial ROS production and cytosolic Ca2+ levels. These findings suggest that SARS-CoV-2 E-protein induces mitochondrial dysfunction, apoptosis, and mtDNA release via VDAC1 modulation. mtDNA that accumulates in the blood activates the cGAS-STING pathway, triggering inflammatory cytokine and chemokine expression that contribute to the cytokine storm and tissue damage seen in cases of severe COVID-19.

Synergistic modulation of SrTiO3-TiO2 colossal permittivity system by internal lattice defects and phase composition: Experimental and theoretical investigations

The SrTiO3–TiO2 composite ceramics with different contents of La doping were fabricated by traditional solid-state sintering methods. The performance of the colossal permittivity ceramics was enhanced by the synergistic design of the internal defect structure and phase composition. When the doping content is 2%, SrTiO3–TiO2 composite ceramics possessed a colossal permittivity (ԑr ∼ 1.1 × 105), low dielectric loss (tanδ ∼ 0.050) and favorable thermal stability (−70 °C-150 °C, ΔC/C25°C ≤ ±15%). Phase structure analysis suggested that a TiO2 secondary phase was induced at the grain boundaries of SrTiO3 phase with the addition of La3+ ions. XPS and dielectric behavior analyses revealed that oxygen vacancies and lattice defects formed by inhomogeneous ion-doping act to modulate the dielectric behavior in ceramics. The IBLC interfacial effects in relation to semiconductor grains and insulation grain boundaries are the main contributors to the colossal permittivity (CP) properties of ceramics, and the contribution of the IBLC effects becomes more prominent with increasing doping content. On the basis of first-principles analysis, the ceramic lattice undergoes severe deformation when the La content is increased, and the gathering of electrons at oxygen vacancies and defects is evident. As a result, it leads to enhanced grain semiconducting properties and interfacial effects, which facilitate colossal permittivity and low dielectric loss for ceramics. The results are prospective in the application of CP ceramics.

Do stress hormones influence choice? A systematic review of pharmacological interventions on the HPA axis and/or SAM system.

The hypothalamus-pituitary-adrenal axis (HPA axis) and the sympathetic-adrenal-medullary system (SAM system), two neuroendocrine systems associated with the stress response, have often been implicated to modulate decision-making in various domains. This systematic review summarizes the scientific evidence on the effects of pharmacological HPA axis and SAM system modulation on decision-making. We found 6375 references, of which 17 studies fulfilled our inclusion criteria. We quantified the risk of bias in our results with respect to missing outcome data, measurements, and selection of the reported results. The included studies administered hydrocortisone, fludrocortisone (HPA axis stimulants), yohimbine, reboxetine (SAM system stimulants), and/or propranolol (SAM system inhibitor). Integrating the evidence, we found that SAM system stimulation had no impact on risk aversion, loss aversion or intertemporal choice, while SAM system inhibition showed a tentative reduction in sensitivity to losses. HPA axis stimulation had no effect on loss aversion or reward anticipation but likely a time-dependent effect on decision under risk. Lastly, combined stimulation of both systems exhibited inconsistent results that could be explained by dose differences (loss aversion) and sex differences (risk aversion). Future research should address time-, dose-, and sex-dependencies of pharmacological effects on decision-making.

On the skew-symmetric binary sequences and the merit factor problem

The merit factor problem is of practical importance to manifold domains, such as digital communications engineering, radars, system modulation, system testing, information theory, physics, chemistry. In this work, some useful mathematical properties related to the flip operation of the skew-symmetric binary sequences are presented. By exploiting those properties, the space complexity of state-of-the-art stochastic merit factor optimization algorithms could be reduced from O(n2) to O(n). As a proof of concept, a lightweight stochastic algorithm was constructed, which can optimize pseudo-randomly generated skew-symmetric binary sequences with long lengths (up to 105+1) to skew-symmetric binary sequences with a merit factor greater than 5. An approximation of the required time is also provided. The numerical experiments suggest that the algorithm is universal and could be applied to skew-symmetric binary sequences with arbitrary lengths.

Reshaped Local and Systemic Immune Responses Triggered by a Biomimetic Multifunctional Nanoplatform Coordinating Multi-Pathways for Cancer Therapy.

Immunotherapy has fundamentally transformed the clinical cancer treatment landscape; however, achieving intricate and multifaceted modulation of the immune systems remains challenging. Here, a multipathway coordination of immunogenic cell death (ICD), autophagy, and indoleamine 2,3-dioxygenase-1 (IDO1) was achieved by a biomimetic nano-immunomodulator assembled from a chemotherapeutic agent (doxorubicin, DOX), small interfering RNA (siRNA) molecules targeting IDO1 (siIDO1), and the zeolitic imidazolate framework-8 (ZIF-8). After being camouflaged with a macrophage membrane, the biomimetic nanosystem, named mRDZ, enriched in tumors, which allowed synergistic actions of its components within tumor cells. The chemotherapeutic intervention led to a compensatory upregulation in the expression of IDO1, consequently exerting an inhibitory effect on the reactive oxygen species (ROS) and autophagic responses triggered by DOX and ZIF-8. Precise gene silencing of IDO1 by siIDO1 alleviated its suppressive influence, thereby facilitating increased ROS production and improved autophagy, ultimately bolstering tumor immunogenicity. mRDZ exhibited strong capability to boost potent local and systemic antitumor immune responses with a feature of memory, which led to the effective suppression of the growth, lung metastasis, and recurrence of the tumor. Serving as an exemplary model for the straightforward and potent reshaping of the immune system against tumors, mRDZ offers valuable insights into the development of immunomodulatory nanomaterials for cancer therapy.

Involvement of the serotonergic, GABAergic and glutamatergic systems of the rostral anterior cingulate cortex in the trait and state anxiety of adult male Wistar rats.

Despite significant advancements to understand of the neural circuitry involved in anxiety, the neurobiology of trait anxiety remains unclear. The rostral anterior cingulate cortex (rACC) and various pathways have been implicated in its regulation, making it a key to trait anxiety. The present study aimed to investigate the role of these neurotransmitter systems in the rACC in trait anxiety. Since trait anxiety is known to modulate state anxiety, we further investigated this relationship. Specifically, in Experiment I, we used animals with high trait anxiety; in Experiment II, we used animals with low trait anxiety; and in Experiment III, we used animals with medium trait anxiety. Before each behavioral assessment, drugs that either increased or decreased serotonergic (Fluoxetine or WAY-100635), GABAergic (Muscimol or Bicuculline), and glutamatergic (NMDA or Ketamine) neurotransmission in the rACC were administered, along with their respective controls. Additionally, in Experiment IV, all animals from the previous experiments were subjected to the Elevated Plus Maze (EPM) and Hole board (HB) test and evaluated without taking into account their trait anxiety levels. The results of the present study showed that, in Exp I, the modulation of the serotonergic, GABAergic and glutamatergic systems in the rACC decreased trait anxiety in highly anxious rats, while by submitting the animals to HB, the administration of fluoxetine increased state anxiety. In Exp II, the modulation of all systems increased trait anxiety in rats with low trait anxiety, whereas, in HB, state anxiety levels were increased with the administration of NMDA. In Exp III, only the modulation of the glutamatergic system, with NMDA, increased both trait and state anxiety levels. However, none of the evaluated neurotransmitter systems altered the state anxiety modeled in the EPM. Overall, the results of the present study provide new insights into the role of the neurotransmitter systems in the rACC in the regulation of trait anxiety and state anxiety.

Effects of serotonergic manipulation in the brainstem and hypothalamus of overnourished rats during lactation

Previous studies suggest that being overweight and obese is capable of altering brain function during critical periods due to the higher plasticity of the brain during development. However, more literature still needs to be on the immediate effect of overnutrition and serotonin modulation in brain areas. In this study, we aimed to evaluate the effects of serotoninergic manipulation on oxidative stress and pro-inflammatory markers in the brainstem and hypothalamus of overnourished rats. The fluoxetine treatment was performed from postnatal day 3 (PND3) to postnatal day 21 (PND21) to evaluate mitochondrial function, oxidative balance, and the mRNA levels of monoaminergic molecules such as serotonin and dopamine, pro-inflammatory cytokines, and BDNF. Neonatal overnutrition induces molecular and biochemical changes in the brainstem and hypothalamus. These nutritional disturbances during lactation dysregulate energy balance and cellular redox, inducing oxidative stress. Conversely, modulation of the serotoninergic system through pharmacological use of fluoxetine was able to reverse the deleterious effects of overnutrition during lactation, enabling better brain development and delaying the development of pathologies and oxidative stress.

LITERATURE REVIEW THE ROLE OF ACUPUNCTURE IN THE MANAGEMENT OF PERIPHERAL NEUROPATHY

Peripheral neuropathy (PN) is a condition characterized by damage to the peripheral nervous system, resulting in symptoms such as pain, numbness, and weakness in the hands and feet. The most common causes include diabetes, thyroid disorders, vitamin B12 deficiency, alcohol abuse, chemotherapy, and human immunodeficiency virus (HIV) infection. Despite the availability of various treatments, neurological disorders remain a significant therapeutic challenge. The therapeutic effects of acupuncture are attributed to several mechanisms, including stimulation of nerve fibers, restoration of blood flow, release of neurotransmitters and hormones, modulation of the autonomic nervous system, anti-inflammatory effects, and increased neuroplasticity. These mechanisms collectively contribute to the relief of symptoms associated with peripheral neuropathy. Evidence suggests that acupuncture is beneficial in treating peripheral neuropathy. Studies have shown that acupuncture can improve nerve conduction study parameters in sensory and motor nerves, reduce neuropathic pain, and improve overall nerve function. Certain acupuncture points such as ST-36, GB-34, SP-3, SP-8, and BI-56 have been identified as particularly effective in managing symptoms of peripheral neuropathy. Although more rigorous studies are needed to fully characterize the effects of acupuncture on peripheral neuropathy, the available evidence supports its use as a complementary therapy. Standardized acupuncture protocols that combine anatomical correlation with peripheral nerves and traditional approaches to neuropathic pain management appear to be effective. Further studies with larger sample sizes and randomized comparisons to sham acupuncture will help establish acupuncture as a guideline for treating peripheral neuropathy. This review outlines the potential of acupuncture as a complementary therapy in the management of peripheral neuropathy.

Rotating magnetic field improves cognitive and memory impairments in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway

Alzheimer's disease (AD) is a geriatric disorder that can be roughly classified into sporadic AD and hereditary AD. The latter is strongly associated with genetic factors, and its treatment poses greater challenges compared to sporadic AD. Rotating magnetic fields (RMF) is a non-invasive treatment known to have diverse biological effects, including the modulation of the central nervous system and aging. However, the impact of RMF on hereditary AD and its underlying mechanism remain unexplored. In this study, we exposed APP/PS1 mice to RMF (2 h/day, 0.2 T, 4 Hz) for a duration of 6 months. The results demonstrated that RMF treatment significantly ameliorated their cognitive and memory impairments, attenuated neuronal damage, and reduced amyloid deposition. Furthermore, RNA-sequencing analysis revealed a significant enrichment of autophagy-related genes and the PI3K/AKT-mTOR signaling pathway. Western blotting further confirmed that RMF activated autophagy and suppressed the phosphorylation of proteins associated with the PI3K/AKT/mTOR signaling pathway in APP/PS1 mice. These protective effects and the underlying mechanism were also observed in Aβ25–35-exposed HT22 cells. Collectively, our findings indicate that RMF improves cognitive and memory dysfunction in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway, thus highlighting the potential of RMF as a clinical treatment for hereditary AD.

Autonomic Nervous System: A Therapeutic Target for Cardiac End-Organ Damage in Hypertension.

More than 1.5 billion people worldwide have arterial hypertension. Hypertension increases the risks of death and cardiovascular disease, such as atrial fibrillation and heart failure. The autonomic nervous system plays an essential role in hypertension development and disease progression. While lifestyle factors, such as obesity and obstructive sleep apnea, predispose to hypertension by increasing sympathetic activity, hypertension itself maintains the autonomic nervous imbalance, providing the substrate for atrial fibrillation and heart failure. Therefore, autonomic nervous system modulation either by direct targeting or indirect treatment of comorbidities has the potential to treat both hypertension and related atrial and ventricular end-organ damage. We discuss interventions for the modulation of the autonomic nervous system for hypertension and related cardiac end-organ damage, including pharmacological adrenergic beta-receptor blockade, renal denervation, carotid baroreceptor stimulation, low-level vagal stimulation, and ablation of ganglionated plexuses. In summary, the literature suggests that targeting the autonomic nervous system potentially represents a therapeutic approach to prevent atrial and ventricular end-organ damage in patients with hypertension. However, clinical trials specifically designed to test the effect of autonomic modulation on hypertension-mediated cardiac end-organ damage are scarce.

Review on Therapeutic Diversity of Oxazole Scaffold: An Update

AbstractOxazole, a five‐membered cyclic ring containing oxygen and nitrogen, displays diverse interactions and structural variations, enhancing its potential applications across various domains. Oxazole derivatives exhibit diverse pharmacological activities, including antidiabetic, anticonvulsant, anticancer, phosphodiesterase inhibition, antiprotozoal, and antibacterial effects, making them appealing to medicinal chemists. Their presence in naturally occurring pharmacologically active substances as well as synthetic medicines underscores their therapeutic potential. This review encompasses recent advancements in the biological activities of oxazole derivatives during the period of 2018–2023. The discussed activities include antitumor, central nervous system (CNS) modulation, antidiabetic, anti‐Alzheimer, antibacterial, and enzyme inhibitory effects. The review highlights the mechanisms of action of these compounds in various diseases, the most potent compounds along with their respective IC50/MIC (inhibitory concentration/minimum inhibitory concentration) values, and discusses the models utilized for quantifying their activity. Currently, there are eight FDA‐approved drugs bearing oxazole scaffolds available in the market. Analysis of the literature reveals that the antitumor activity of oxazole derivatives is particularly noteworthy among their various activities. The incorporation of phenyl, methoxyphenyl, or halogen‐substituted phenyl moieties significantly enhances therapeutic activities compared to reference drugs. The substitution flexibility at three positions of oxazole derivatives contributes to their spectrum of pharmacological activities.