Comparative Study between the Diagnostic Effectiveness of Brain SPECT with [123I]Ioflupane and [123I]MIBG Scintigraphy in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease. It has a fast progression, so early diagnosis is decisive. Two functional imaging tests can be involved in its diagnosis: [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. Our aim is to comparatively analyze the diagnostic performance of both techniques. METHODS: 46 patients (24 males and 22 females) with MSA underwent [123I]Ioflupane SPECT and [123I]MIBG scintigraphy. In each of these techniques, qualitative assessment was compared with quantitative assessment. RESULTS: SPECT visual assessment was positive in 93.5% of subjects (S = 95.24%; PPV = 93.02%). A cut-off of 1.363 was established for overall S/O index (S = 85.7%, E = 100%). Visual assessment of scintigraphy was positive in 73.1% (S = 78.57%, PPV = 94.29%). For the delayed heart/medistinum ratio (HMR) a cut-off of 1.43 (S = 85.3, E = 100%) was obtained. For each unit increase in delayed HMR, the suspicion of MSA increased by 1.58 (OR = 1.58, p < 0.05). The quantitative assessment showed an association with the visual assessment for each technique (p < 0.05). CONCLUSIONS: Both tests are useful in MSA diagnosis. Comparatively, we did not observe a clear superiority of either. Striatal and myocardial deterioration do not evolve in parallel. Qualitative assessment is crucial in both techniques, together with the support of quantitative analysis. Delayed HMR shows a direct relationship with the risk of MSA.

Neuroprotective and antioxidant effects of docosahexaenoic acid (DHA) in an experimental model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease, whose etiology is not yet fully understood, although there are several factors that can increase the chances of suffering from it. These factors include nutrition, which may be involved in the pathogenesis of the disease. In relation to nutrition, docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), has emerged as an important player in the regulation of neuroinflammation, being considered a pleiotropic molecule. This study aimed to evaluate the effect of DHA supplementation on clinical state and oxidative stress produced by experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Twenty-five Dark Agouti rats which were used divided into Control Group, Control+Vehicle Group, Control+DHA Group, EAE Group, and EAE+DHA Group. DHA was administered for 51 days by intraperitoneal (i.p.) injection at a dose of 40 mg/kg, once a day, 5 days a week. DHA supplementation produced a decrease in oxidative stress, as well as an improvement in the clinical score of the disease. DHA could exert a beneficial effect on the clinic of MS, through the activation of the antioxidant factor Nrf2.

Sodium chloride-induced changes in oxidative stress, inflammation, and dysbiosis in experimental multiple sclerosis.

Objectives: The high-salt diet (HSD) has been associated with cognitive dysfunction by attacking the cerebral microvasculature, through an adaptive response, initiated in the intestine and mediated by Th17 cells. In the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), it has been described that NaCl causes an increase in T cell infiltration in the central nervous system. NaCl also promotes macrophage response and Th17 cell differentiation, worsening the course of the disease. HSD may trigger an activation of the immune system and enhance inflammation. However, certain studies not only do not support this possibility, but support the opposite, as the effect of salt on immune cells may not necessarily be pathogenic. Therefore, this study aimed to evaluate the effect of an over intake of salt in rats with EAE, based on the clinical course, oxidative stress, markers of inflammation and the gut dysbiosis.Methods: 15 Dark Agouti rats were used, which were divided into control group, EAE group and EAE + NaCl group. Daily 0.027 g of NaCl dissolved in 300 µl of H2O was administered through a nasogastric tube for 51 days.Results: NaCl administration produced an improvement in clinical status and a decrease in biomarkers of oxidative stress, inflammation, and dysbiosis.Conclusion: The underlying mechanism by which NaCl causes these effects could involve the renin-angiotensin-aldosterone system (RAAS), which is blocked by high doses of salt.

Follow-Up Findings in Multiple System Atrophy from [123I]Ioflupane Single-Photon Emission Computed Tomography (SPECT): A Prospective Study.

BACKGROUND: Multiple system atrophy (MSA) is subdivided into two types: MSA-P (parkinsonian) and MSA-C (cerebellar). Brain SPECT allows for the detection of nigrostriatal involvement, even in the early stages. To date, the scientific literature does not show a consensus on how to follow-up MSA, especially MSA-C. Our aim was to analyze the diagnostic effectiveness of repeat [123I]Ioflupane SPECT for the follow-up of MSA. METHODS: A longitudinal observational study on 22 MSA patients (11 males and 11 females). RESULTS: Significant changes were obtained in the quantitative SPECT assessments in the three Striatum/Occipital indices. The qualitative SPECT diagnosis did not show differences between the initial and evolving SPECT, but the neurologist's clinical suspicion did. Our results showed a brain deterioration of around 31% at 12 months, this being the optimal cut-off for differentiating a diseased subject (capable of solving diagnostic error rate). Previous imaging tests were inconclusive, as they showed less deterioration in the SPECT and quantitative assessments with respect to the group of confirmed patients. Repeated SPECT increased the diagnostic sensitivity (50% vs. 75%) and positive predictive value (72.73% vs. 77%). In addition, repeated SPECT proved decisive in the diagnosis of initial inconclusive cases. CONCLUSION: Repeat SPECT at 12 months proves useful in the diagnosis and follow-up of MSA.

Effect of the Combination of Different Therapies on Oxidative Stress in the Experimental Model of Multiple Sclerosis.

Oxidative stress is heavily involved in several pathological features of Multiple Sclerosis (MS), such as myelin destruction, axonal degeneration, and inflammation. Different therapies have been shown to reduce the oxidative stress that occurs in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Some of these therapies are transcranial magnetic stimulation (TMS), extra virgin olive oil (EVOO) and S-allyl cysteine (SAC). This study aims to test the antioxidant effect of these three therapies, to compare the efficacy of SAC versus TMS and EVOO, and to analyze the effect of combining SAC + TMS and SAC and EVOO. Seventy Dark Agouti rats were used, which were divided into Control group; Vehicle group; Mock group; SAC; EVOO; TMS; SAC + EVOO; SAC + TMS; EAE; EAE + SAC; EAE + EVOO; EAE + TMS; EAE + SAC + EVOO; EAE + SAC + TMS. The TMS consisted of an oscillatory magnetic field in the form of a sine wave with a frequency of 60 Hz and an amplitude of 0.7mT (EL-EMF) applied for two hours in the morning, once a day, five days a week. SAC was administered at a dose of 50 mg/kg body weight, orally daily, five days a week. EVOO represented 10% of their calorie intake in the total standard daily diet of rats AIN-93G. All treatments were maintained for 51 days. TMS, EVOO and SAC, alone or in combination, reduce oxidative stress, increasing antioxidant defenses and also lowering the clinical score. Combination therapies do not appear to be more potent than individual therapies against the oxidative stress of EAE or its clinical symptoms.

Prevalence of Active Primitive Reflexes and Craniosacral Blocks in Apparently Healthy Children and Relationships with Neurodevelopment Disturbances.

BACKGROUND: In healthy children, the frequency of the anomalous persistence of primitive reflexes (PRs) and craniosacral blocks (CBs) is unknown, as well as their impact on neurodevelopment, behaviour disorders and related consequences. We aim to know the prevalence of anomalous PRs and CBs in apparently healthy children and their relationships with behavior and neurodevelopment anomalies. METHODS: Participants (n = 120) were evaluated via a physical examination to detect PRs and CBs and an ad hoc parent survey to collect perinatal events, and children's behavioral assessments were conducted by teachers using the Battelle score. RESULTS: PRs were present in 89.5%. Moro (70.8%), cervical asymmetric (78.3%) and cervical symmetric PRs (67.5%) were the most frequently observed PRs. CBs were found in 83.2%, and the most frequent CBs were dura mater (77.5%) and sphenoid bone (70%) blocks. Moro, cervical asymmetric and cervical symmetric active primitive reflexes were significantly associated with cranial blocks of dura mater, parietal zones and sphenoid bone sway. Gestational disorders or perinatal complications were associated with a higher frequency of PRs and CBs. The presence of PRs and CBs was associated with abnormal Battelle scores and neurobehavioral problems. CONCLUSION: The presence of PRs and CBs in children without diagnosed diseases is frequent and related to disturbances in childhood neurodevelopment.

Diagnostic Effectiveness of [123I]Ioflupane Single Photon Emission Computed Tomography (SPECT) in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder that has no curative treatment. Diagnosis is based on a set of criteria established by Gilman (1998 and 2008) and recently updated by Wenning (2022). We aim to determine the effectiveness of [123I]Ioflupane SPECT in MSA, especially at the initial clinical suspicion. METHODS: A cross-sectional study of patients at the initial clinical suspicion of MSA, referred for [123I]Ioflupane SPECT. RESULTS: Overall, 139 patients (68 men, 71 women) were included, 104 being MSA-probable and 35 MSA-possible. MRI was normal in 89.2%, while SPECT was positive in 78.45%. SPECT showed high sensitivity (82.46%) and positive predictive value (86.24), reaching maximum sensitivity in MSA-P (97.26%). Significant differences were found when relating both SPECT assessments in the healthy-sick and inconclusive-sick groups. We also found an association when relating SPECT to the subtype (MSA-C or MSA-P), as well as to the presence of parkinsonian symptoms. Lateralization of striatal involvement was detected (left side). CONCLUSIONS: [123I]Ioflupane SPECT is a useful and reliable tool for diagnosing MSA, with good effectiveness and accuracy. Qualitative assessment shows a clear superiority when distinguishing between the healthy-sick categories, as well as between the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes at initial clinical suspicion.

CCR6 as a Potential Target for Therapeutic Antibodies for the Treatment of Inflammatory Diseases.

The CC chemokine receptor 6 (CCR6) is a G protein-coupled receptor (GPCR) involved in a wide range of biological processes. When CCR6 binds to its sole ligand CCL20, a signaling network is produced. This pathway is implicated in mechanisms related to many diseases, such as cancer, psoriasis, multiple sclerosis, HIV infection or rheumatoid arthritis. The CCR6/CCL20 axis plays a fundamental role in immune homeostasis and activation. Th17 cells express the CCR6 receptor and inflammatory cytokines, including IL-17, IL-21 and IL-22, which are involved in the spread of inflammatory response. The CCL20/CCR6 mechanism plays a crucial role in the recruitment of these pro-inflammatory cells to local tissues. To date, there are no drugs against CCR6 approved, and the development of small molecules against CCR6 is complicated due to the difficulty in screenings. This review highlights the potential as a therapeutic target of the CCR6 receptor in numerous diseases and the importance of the development of antibodies against CCR6 that could be a promising alternative to small molecules in the treatment of CCR6/CCL20 axis-related pathologies.

SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19.

The SARS-CoV-2 pandemic has raised particular concern for people with Multiple Sclerosis, as these people are believed to be at increased risk of infection, especially those being treated with disease-modifying therapies. Therefore, the objective of this review was to describe how COVID-19 affects people who suffer from Multiple Sclerosis, evaluating the risk they have of suffering an infection by this virus, according to the therapy to which they are subjected as well as the immune response of these patients both to infection and vaccines and the neurological consequences that the virus can have in the long term. The results regarding the increased risk of infection due to treatment are contradictory. B-cell depletion therapies may cause patients to have a lower probability of generating a detectable neutralizing antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes.

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action.

BACKGROUND: Melatonin is an indole hormone secreted primarily by the pineal gland that showing anti-oxidant, anti-inflammatory and anti-apoptotic capacity. It can play an important role in the pathophysiological mechanisms of various diseases. In this regard, different studies have shown that there is a relationship between Melatonin and Multiple Sclerosis (MS). MS is a chronic immune-mediated disease of the Central Nervous System. AIM: The objective of this review was to evaluate the mechanisms of action of melatonin on oxidative stress, inflammation and intestinal dysbiosis caused by MS, as well as its interaction with different hormones and factors that can influence the pathophysiology of the disease. RESULTS: Melatonin causes a significant increase in the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione and can counteract and inhibit the effects of the NLRP3 inflammasome, which would also be beneficial during SARS-CoV-2 infection. In addition, melatonin increases antimicrobial peptides, especially Reg3ß, which could be useful in controlling the microbiota. CONCLUSION: Melatonin could exert a beneficial effect in people suffering from MS, running as a promising candidate for the treatment of this disease. However, more research in human is needed to help understand the possible interaction between melatonin and certain sex hormones, such as estrogens, to know the potential therapeutic efficacy in both men and women.

Neural Network Aided Detection of Huntington Disease.

Huntington Disease (HD) is a degenerative neurological disease that causes a significant impact on the quality of life of the patient and eventually death. In this paper we present an approach to create a biomarker using as an input DNA CpG methylation data to identify HD patients. DNA CpG methylation is a well-known epigenetic marker for disease state. Technological advances have made it possible to quickly analyze hundreds of thousands of CpGs. This large amount of information might introduce noise as potentially not all DNA CpG methylation levels will be related to the presence of the illness. In this paper, we were able to reduce the number of CpGs considered from hundreds of thousands to 237 using a non-linear approach. It will be shown that using only these 237 CpGs and non-linear techniques such as artificial neural networks makes it possible to accurately differentiate between control and HD patients. An underlying assumption in this paper is that there are no indications suggesting that the process is linear and therefore non-linear techniques, such as artificial neural networks, are a valid tool to analyze this complex disease. The proposed approach is able to accurately distinguish between control and HD patients using DNA CpG methylation data as an input and non-linear forecasting techniques. It should be noted that the dataset analyzed is relatively small. However, the results seem relatively consistent and the analysis can be repeated with larger data-sets as they become available.

An Entropy Approach to Multiple Sclerosis Identification.

Multiple sclerosis (MS) is a relatively common neurodegenerative illness that frequently causes a large level of disability in patients. While its cause is not fully understood, it is likely due to a combination of genetic and environmental factors. Diagnosis of multiple sclerosis through a simple clinical examination might be challenging as the evolution of the illness varies significantly from patient to patient, with some patients experiencing long periods of remission. In this regard, having a quick and inexpensive tool to help identify the illness, such as DNA CpG (cytosine-phosphate-guanine) methylation, might be useful. In this paper, a technique is presented, based on the concept of Shannon Entropy, to select CpGs as inputs for non-linear classification algorithms. It will be shown that this approach generates accurate classifications that are a statistically significant improvement over using all the data available or randomly selecting the same number of CpGs. The analysis controlled for factors such as age, gender and smoking status of the patient. This approach managed to reduce the number of CpGs used while at the same time significantly increasing the accuracy.

Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial.

This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another.

Development of a High-Throughput Calcium Mobilization Assay for CCR6 Receptor Coupled to Hydrolase Activity Readout.

CCR6 is a chemokine receptor highly implicated in inflammatory diseases and could be a potential therapeutic target; however, no therapeutic agents targeting CCR6 have progressed into clinical evaluation. Development of a high-throughput screening assay for CCR6 should facilitate the identification of novel compounds against CCR6. To develop a cell-based assay, RBL-2H3 cells were transfected with plasmids encoding ß-hexosaminidase and CCR6. Intracellular calcium mobilization of transfected cells was measured with a fluorescent substrate using the activity of released hexosaminidase as readout of the assay. This stable, transfected cell showed a specific signal to the background ratio of 19.1 with low variability of the signal along the time. The assay was validated and optimized for high-throughput screening. The cell-based calcium mobilization assay responded to the specific CCR6 ligand, CCL20, in a dose-dependent manner with an EC50 value of 10.72 nM. Furthermore, the assay was deemed robust and reproducible with a Z' factor of 0.63 and a signal window of 7.75. We have established a cell-based high-throughput calcium mobilization assay for CCR6 receptor. This assay monitors calcium mobilization, due to CCR6h activation by CCL20, using hexosaminidase activity as readout. This assay was proved to be robust, easy to automate and could be used as method for screening of CCR6 modulators.

Hypoxia preconditioning increases the ability of healthy but not diabetic rat-derived adipose stromal/stem cells (ASC) to improve histological lesions of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality. These findings related to the hypoxia preconditioning ability to enhance adipose-tissue derived-MSC (ASC) performance have led us to wonder if hypoxia could increase the known beneficial effect of normal ASC in DN and if it could correct the expected inability of diabetic rat-derived ASC to exert this effect in vivo. To answer these questions, in the present study we have used ASC from healthy and diabetic-induced rats, cultured under standard conditions or hypoxia preconditioned, in a DN rat model induced by streptozotocin (STZ). METHODS: Diabetes was induced in Wistar-rats by 60 mg/kg streptozotocin (STZ) intraperitoneal injection. Fifteen days thereafter, five diabetic-induced rats and five healthy, previously injected with saline, were sacrificed and used as ASC donors . Both healthy and diabetic rat-derived ASC (cASC and dASC, respectively) were cultured under standard conditions (21%O2)(N) or were subjected to a 48 h conditioning period in hypoxia (3%O2)(H). Thus, four types of cells were generated depending on their origin (healthy or diabetic-induced rats) and the culture conditions(N or H):cASC-N, cASC-H, dASC-N and dASC-H. DN experimental study were carried out fifteen days after STZ induction of diabetes in fifty-two healthy rats. DN-induced-animals were randomly assigned to be injected with 200 µL saline as placebo or with 3 × 106 cASC-N, cASC-H, dASC-N or dASC-H, according to the study group. Serum glucose, urea and creatinine, and urine albumin levels were measured at 2-weeks intervals until day+ 45 after ND-induction.Animals were sacrificed and kidneys extracted for histopathological and transmission electron microcopy analysis RESULTS: None of the four study groups that received cell treatment showed significant changes in serum glucose, urea and creatinine levels, urine albumin concentration and body weight compared to placebo ND-induced group. Interestingly, only the group that received cASC-H showed a reduction in glucose and creatinine levels although it did not reach statistical significance.All DN-induced groups treated with ASC reduced significantly renal lesions such as mesangial expansion, mesangiolysis, microaneurysms and acute tubular necrosis compared to ND-induced placebo group (p ≤ 0.05). Renal injuries such as clear tubular cell changes, thickening of tubular basement membrane, tubular cysts and interstitial fibrosis significantly showed reduction in ND-induced rats treated with cASC-H regarding to their received cASCN (p ≤ 0.05). Non statistical differences were observed in the improvement capacity of cASC and dASC culture under standard condition.However, hypoxia preconditioning reduces the presence of tubular cysts (p ≤ 0.01). CONCLUSIONS: Hypoxia preconditioning enhances the ability of healthy rat-derived ASC to improve kidney injury in a rat model of DN. Moreover, diabetic-derived ASC exhibits a similar ability to healthy ASC which is clearly more than expected, but it is not significantly modified by hypoxia preconditioning.

Lactose and Casein Cause Changes on Biomarkers of Oxidative Damage and Dysbiosis in an Experimental Model of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Experimental Autoimmune Encephalomyelitis (EAE) in rats closely reproduces Multiple Sclerosis (MS), a disease characterized by neuroinflammation and oxidative stress that also appears to extend to other organs and their compartments. The origin of MS is a matter for discussion, but it would seem that altering certain bacterial populations present in the gut may lead to a proinflammatory condition due to the bacterial Lipopolysaccharides (LPS) in the so-called brain-gut axis. The casein and lactose in milk confer anti-inflammatory properties and immunomodulatory effects. The objectives of this study were to evaluate the effects of administration of casein and lactose on the oxidative damage and the clinical status caused by EAE and to verify whether both casein and lactose had any effect on the LPS and its transport protein -LBP-. METHODS: Twenty male Dark Agouti rats were divided into control rats (control), EAE rats, and EAE rats, to which casein and lactose, EAE+casein, and EAE+lactose, respectively, were administered. Fifty-one days after casein and lactose administration, the rats were sacrificed, and different organs were studied (brain, spinal cord, blood, heart, liver, kidney, small, and large intestine). In the latter, products derived from oxidative stress were studied (lipid peroxides and carbonylated proteins) as well as the glutathione redox system, various inflammation factors (total nitrite, Nuclear Factor-kappa B p65, the Rat Tumour Necrosis Factor-α), and the LPS and LBP values. RESULTS AND CONCLUSION: Casein and lactose administration improved the clinical aspect of the disease at the same time as reducing inflammation and oxidative stress, exerting its action on the glutathione redox system, or increasing GPx levels.

Mechanisms Involved in Neuroprotective Effects of Transcranial Magnetic Stimulation.

Transcranial Magnetic Stimulation (TMS) is widely used in neurophysiology to study cortical excitability. Research over the last few decades has highlighted its added value as a potential therapeutic tool in the treatment of a broad range of psychiatric disorders. More recently, a number of studies have reported beneficial and therapeutic effects for TMS in neurodegenerative conditions and strokes. Yet, despite its recognised clinical applications and considerable research using animal models, the molecular and physiological mechanisms through which TMS exerts its beneficial and therapeutic effects remain unclear. They are thought to involve biochemical-molecular events affecting membrane potential and gene expression. In this aspect, the dopaminergic system plays a special role. This is the most directly and selectively modulated neurotransmitter system, producing an increase in the flux of dopamine (DA) in various areas of the brain after the application of repetitive TMS (rTMS). Other neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA) have shown a paradoxical response to rTMS. In this way, their levels increased in the hippocampus and striatum but decreased in the hypothalamus and remained unchanged in the mesencephalon. Similarly, there are sufficient evidence that TMS up-regulates the gene expression of BDNF (one of the main brain neurotrophins). Something similar occurs with the expression of genes such as c-Fos and zif268 that encode trophic and regenerative action neuropeptides. Consequently, the application of TMS can promote the release of molecules involved in neuronal genesis and maintenance. This capacity may mean that TMS becomes a useful therapeutic resource to antagonize processes that underlie the previously mentioned neurodegenerative conditions.

Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder.

Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.

Evolution of Metabolic Phenotypes of Obesity in Coronary Patients after 5 Years of Dietary Intervention: From the CORDIOPREV Study.

BACKGROUND: Obesity phenotypes with different metabolic status have been described previously. We analyzed metabolic phenotypes in obese coronary patients during a 5-year follow-up, and examined the factors influencing this evolution. METHODS: The CORDIOPREV study is a randomized, long-term secondary prevention study with two healthy diets: Mediterranean and low-fat. All obese patients were classified as either metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO). We evaluated the changes in the metabolic phenotypes and related variables after 5 years of dietary intervention. RESULTS: Initially, 562 out of the 1002 CORDIOPREV patients were obese. After 5 years, 476 obese patients maintained their clinical and dietary visits; 71.8% of MHO patients changed to unhealthy phenotypes (MHO-Progressors), whereas the MHO patients who maintained healthy phenotypes (MHO-Non-Progressors) lost more in terms of their body mass index (BMI) and had a lower fatty liver index (FLI-score) (p < 0.05). Most of the MUO (92%) patients maintained unhealthy phenotypes (MUO-Non-Responders), but 8% became metabolically healthy (MUO-Responders) after a significant decrease in their BMI and FLI-score, with improvement in all metabolic criteria. No differences were found among dietary groups. CONCLUSIONS: A greater loss of weight and liver fat is associated with a lower progression of the MHO phenotype to unhealthy phenotypes. Likewise, a marked improvement in these parameters is associated with regression from MUO to healthy phenotypes.

Gene and cell therapy and nanomedicine for the treatment of multiple sclerosis: bibliometric analysis and systematic review of clinical outcomes.

INTRODUCTION: Continuous improvement in cellular and molecular biology has led to the development of diverse advanced therapies. These include cell therapy and gene therapy, among others. Nanomedicine can also be used for therapeutic purposes. AREAS COVERED: The author carried out a bibliometric analysis to find out about the biomedical literature in these therapies applied to multiple sclerosis (MS) and its chronological evolution, from a quantitative and qualitative point of view. After this, articles which were identified as clinical trials were retrieved full-text and examined for further evaluation of their evidence-based level according to the CASP scale. In the bibliometric analysis the authors retrieved 2,791 studies, from which 2,405 were about cell therapy, 194 about gene therapy and 192 about nanomedicine; scientific production in these areas has been progressive and growing in terms of quantity and quality. In the systematic review 39 trials were retrieved, all of them about cell therapy, which had relevant sample sizes. The average of scientific-quality was good or very good (about 9/11 points). EXPERT OPINION: There is a class I evidence supporting the effectiveness of cell therapy as safe therapeutic option in multiple sclerosis with health benefits in the medium and long term.