ABSTRACT
Objective: This study aimed to evaluate physical skin changes and patients' subjective perception of treatment with photothermal bioactivated platelet-rich plasma (MCT Plasma) for hand rejuvenation. Background: Age-related changes in the dorsum of the hand include volume loss, dyschromia, and soft-tissue atrophy, which result in wrinkles and prominent deep structures. Methods: We conducted a prospective, single-center, randomized pilot study on 10 healthy female volunteers from 30 to 65 years with hand aging signs. Patients received two sessions of MCT Plasma on the treated hand and two sessions of standard platelet-rich plasma (PRP) on the control hand. Results were assessed through high-frequency ultrasonography, photographs, a patient satisfaction survey, patient perception of skin aspect, and patient perception of amelioration survey. Results: Ten women with a mean age of 57.5 years (standard deviation 10.5, range 31 - 67) were included, and seven (70%) completed the study. The treated hands' skin subepidermal low-echogenic band (SLEB) decreased from 20% to 60%, and 57.1% (n = 4) had better results than control. Twenty percent of patients were very satisfied with the results, 40% were satisfied, 40% were neutral, and none were unsatisfied or very unsatisfied. Patients perceived the skin of the treated hand (MCT Plasma) as "much better" (20%), "better" (60%), and "no changes" (20%) compared with the skin of the control hand (standard PRP). No treatment-related adverse events were reported during the study. Conclusions: Hands treated with MCT Plasma tended to have better outcomes in reducing SLEB compared with those treated with standard PRP. Patients were satisfied and the treatment was safe with no technical complications. However, further randomized controlled trials with larger sample sizes are mandatory to validate the extent of improvement provided by this device based on photothermal biomodulation.
Subject(s)
Hand , Platelet-Rich Plasma , Rejuvenation , Skin Aging , Humans , Female , Pilot Projects , Middle Aged , Prospective Studies , Skin Aging/radiation effects , Adult , Aged , Patient Satisfaction , Photothermal Therapy , Treatment OutcomeABSTRACT
Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and the 5-AZA group. Inflammation increases miRNs and, specifically, miR-18a, miR-21 and miR-34a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRN profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRN expression levels. Relating to prognostic risk factors, high-risk MDS groups (high Revised International Prognostic Scoring System (IPSS-R), high cytogenetic risk, high molecular risk (HMR) mutations) tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRN expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.
Subject(s)
Inflammation , MicroRNAs , Myelodysplastic Syndromes , Humans , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/drug therapy , MicroRNAs/genetics , MicroRNAs/blood , Male , Female , Middle Aged , Aged , Inflammation/genetics , Azacitidine/pharmacology , Adult , Aged, 80 and over , Oxidative Stress , Case-Control Studies , PrognosisABSTRACT
Protein glycosylation is a post-translational modification involved in wide range of biological processes. In mammalian spermatozoa this modification has been identified in numerous proteins, and membrane glycoproteins are involved in the fertilization process. The objective of the present study was to identify changes in protein glycosylation after acrosome reaction (AR) induction using the 4-Br-A23187 ionophore. Our results showed that treatment with 10 µM of 4-Br-A23187 for 20 min significantly increased the percentage of live acrosome-reacted spermatozoa compared to the control (69.8 ± 0.8 vs. 6.4 ± 0.5; mean % ± SEM, respectively). Also, we observed an increase in 32 kDa tyrosine-phosphorylated protein (p32) and a decrease in serine/threonine phosphorylation of the protein kinase A substrates (phospho-PKA-substrates) after ionophore treatment. Furthermore, changes in glycosylated proteins following AR induction were analyzed using different HRP-conjugated lectins (GNA, DSA, and SNA), revealing changes in mannose and sialic acid residues. Proteomic analysis of isolated proteins using GNA lectin revealed that 50 proteins exhibited significantly different abundance (q-value < 0.01). Subsequent analysis using Uniprot database identified 39 downregulated and 11 upregulated proteins in the presence of 4-Br-A23187. Notably, six of these proteins were classified as transmembrane proteins, namely LRRC37A/B like protein 1 C-terminal domain-containing protein, Membrane metalloendopeptidase like 1, VWFA domain-containing protein, Syndecan, Membrane spanning 4-domains A14 and Serine protease 54. This study shows a novel protocol to induce acrosome reaction in boar spermatozoa and identifies new transmembrane proteins containing mannose residues. Further work is needed to elucidate the role of these proteins in sperm-oocyte fusion.
Subject(s)
Acrosome Reaction , Calcimycin , Spermatozoa , Animals , Male , Acrosome Reaction/drug effects , Swine , Spermatozoa/metabolism , Spermatozoa/drug effects , Calcimycin/pharmacology , Glycoproteins/metabolism , Glycosylation , Proteome , Calcium Ionophores/pharmacologyABSTRACT
Samarium (Sm) is a rare-earth element recently included in the list of critical elements due to its vital role in emerging new technologies. With an increasing demand for Sm, microbial bioremediation may provide a cost-effective and a more ecologically responsible alternative to remove and recover Sm. We capitalized on a previously selected Chlamydomonas reinhardtii strain tolerant to Sm (1.33 × 10-4 M) and acidic pH and carried out settling selection to increase the Sm uptake performance. We observed a rapid response to selection in terms of cellular phenotype. Cellular size decreased and circularity increased in a stepwise manner with every cycle of selection. After four cycles of selection, the derived CSm4 strain was significantly smaller and was capable of sequestrating 41% more Sm per cell (1.7 × 10-05 ± 1.7 × 10-06 ng) and twice as much Sm in terms of wet biomass (4.0 ± 0.4 mg Sm · g-1) compared to the ancestral candidate strain. The majority (~70%) of the Sm was bioaccumulated intracellularly, near acidocalcisomes or autophagic vacuoles as per TEM-EDX microanalyses. However, Sm analyses suggest a stronger response toward bioabsorption resulting from settling selection. Despite working with Sm and pH-tolerant strains, we observed an effect on fitness and photosynthesis inhibition when the strains were grown with Sm. Our results clearly show that phenotypic selection, such as settling selection, can significantly enhance Sm uptake. Laboratory selection of microalgae for rare-earth metal bioaccumulation and sorption can be a promising biotechnological approach.
Subject(s)
Chlamydomonas reinhardtii , Chlamydomonas reinhardtii/metabolism , Chlamydomonas reinhardtii/genetics , Biodegradation, Environmental , Selection, GeneticABSTRACT
We report two novel prodrug Pt(IV) complexes with bis-organosilane ligands in axial positions: cis-dichloro(diamine)-trans-[3-(triethoxysilyl)propylcarbamate]platinum(IV) (Pt(IV)-biSi-1) and cis-dichloro(diisopropylamine)-trans-[3-(triethoxysilyl) propyl carbamate]platinum(IV) (Pt(IV)-biSi-2). Pt(IV)-biSi-2 demonstrated enhanced in vitro cytotoxicity against colon cancer cells (HCT 116 and HT-29) compared with cisplatin and Pt(IV)-biSi-1. Notably, Pt(IV)-biSi-2 exhibited higher cytotoxicity toward cancer cells and lower toxicity on nontumorigenic intestinal cells (HIEC6). In preclinical mouse models of colorectal cancer, Pt(IV)-biSi-2 outperformed cisplatin in reducing tumor growth at lower concentrations, with reduced side effects. Mechanistically, Pt(IV)-biSi-2 induced permanent DNA damage independent of p53 levels. DNA damage such as double-strand breaks marked by histone gH2Ax was permanent after treatment with Pt(IV)-biSi-2, in contrast to cisplatin's transient effects. Pt(IV)-biSi-2's faster reduction to Pt(II) species upon exposure to biological reductants supports its superior biological response. These findings unveil a novel strategy for designing Pt(IV) anticancer prodrugs with enhanced activity and specificity, offering therapeutic opportunities beyond conventional Pt drugs.
Subject(s)
Antineoplastic Agents , Organoplatinum Compounds , Prodrugs , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/chemical synthesis , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Ligands , Mice , Cell Line, Tumor , Silanes/chemistry , Silanes/pharmacology , Structure-Activity Relationship , Drug Screening Assays, Antitumor , HT29 CellsSubject(s)
Astrocytes , Caudate Nucleus , Gait Disorders, Neurologic , Motor Cortex , Neuronal Plasticity , Parkinson Disease , Transcranial Magnetic Stimulation , Humans , Parkinson Disease/therapy , Parkinson Disease/complications , Parkinson Disease/physiopathology , Neuronal Plasticity/physiology , Motor Cortex/physiopathology , Male , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/physiopathology , Middle Aged , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/therapy , Female , Aged , Postural Balance/physiology , Sensation Disorders/etiology , Sensation Disorders/therapy , Sensation Disorders/physiopathologyABSTRACT
The development of slippery surfaces has been widely investigated due to their excellent icephobic properties. A distinct kind of an ice-repellent structure known as a slippery liquid-infused porous surface (SLIPS) has recently drawn attention due to its simplicity and efficacy as a passive ice-protection method. These surfaces are well known for exhibiting very low ice adhesion values (τice < 20 kPa). In this study, pure Polytetrafluoroethylene (PTFE) fibers were fabricated using the electrospinning process to produce superhydrophobic (SHS) porous coatings on samples of the aeronautical alloy AA6061-T6. Due to the high fluorine-carbon bond strength, PTFE shows high resistance and chemical inertness to almost all corrosive reagents as well as extreme hydrophobicity and high thermal stability. However, these unique properties make PTFE difficult to process. For this reason, to develop PTFE fibers, the electrospinning technique has been used by an PTFE nanoparticles (nP PTFE) dispersion with addition of a very small amount of polyethylene oxide (PEO) followed with a sintering process (380 °C for 10 min) to melt the nP PTFE together and form uniform fibers. Once the porous matrix of PTFE fibers is attached, lubricating oil is added into the micro/nanoscale structure in the SHS in place of air to create a SLIPS. The experimental results show a high-water contact angle (WCA) ≈ 150° and low roll-off angle (αroll-off) ≈ 22° for SHS porous coating and a decrease in the WCA ≈ 100° and a very low αroll-off ≈ 15° for SLIPS coating. On one hand, ice adhesion centrifuge tests were conducted for two types of icing conditions (glaze and rime) accreted in an ice wind tunnel (IWT), as well as static ice at different ice adhesion centrifuge test facilities in order to compare the results for SHS, SLIPs and reference materials. This is considered a preliminary step in standardization efforts where similar performance are obtained. On the other hand, the ice adhesion results show 65 kPa in the case of SHS and 4.2 kPa of SLIPS for static ice and <10 kPa for rime and glace ice. These results imply a significant improvement in this type of coatings due to the combined effect of fibers PTFE and silicon oil lubricant.
ABSTRACT
We aimed to investigate the impact of processing boar spermatozoa with phosphate-buffered saline (PBS) at 4 ËC on acrosomal integrity and increase in 32 kDa tyrosine-phosphorylated protein (p32). Following cooled PBS washing, we observed a significant increase in p32 levels and in the proportion of dead spermatozoa with compromised acrosomal integrity compared to sperm washing using PBS at room temperature. Interestingly, this increase in p32 was effectively inhibited when cooled PBS was supplemented with 1 mM AEBSF, a serine protease inhibitor. Our findings suggest that the increase of p32 in response to cooled PBS washing in boar spermatozoa is associated with enhanced protease activity in dead spermatozoa.
Subject(s)
Phosphates , Spermatozoa , Animals , Male , Phosphates/metabolism , Phosphates/pharmacology , Semen , Spermatozoa/physiology , Swine , Tyrosine/metabolismABSTRACT
Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten intake. Celiac hepatitis is the most common hepatic manifestation of CD, it usually responds to a gluten-free diet (GFD) and is sometimes the only manifestation in paucisymptomatic CD. Through this descriptive observational study, we determined the prevalence of liver abnormalities upon diagnosis of CD. A total of 140 patients were included. The prevalence of alterations in liver markers at diagnosis of CD was 47%. In 2.9% of patients, liver abnormalities were the only manifestation at diagnosis. A higher prevalence of liver alterations was found in those patients who presented a more severe histological alteration (MARSH 3c).
Subject(s)
Celiac Disease , Inflammatory Bowel Diseases , Liver Diseases , Humans , Celiac Disease/complications , Celiac Disease/diagnosis , Celiac Disease/epidemiology , Liver Diseases/epidemiology , Liver Diseases/etiology , Diet, Gluten-Free , BiopsyABSTRACT
Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.
ABSTRACT
PURPOSE: To evaluate the impact of UI TEAM RX, a pharmacy-based enhanced services and care model, on adherence in patients with hypertension and prescribed a renin-angiotensin system antagonist (RASA). METHODS: A single-center, retrospective, observational cohort study was conducted in an academic health system, University of Illinois Hospital & Health Sciences System (UI Health). The cohort consisted of patients who utilized UI Health's outpatient pharmacies between May 2016 and December 2018 to fill RASA prescriptions. Patients who were not part of the UI TEAM RX care model served as the control group, while patients enrolled in UI TEAM RX formed the intervention group. The control and intervention groups were matched based on index date, age, gender, and race. The primary outcome was mean change in a rolling 6-month calculation of proportion of days covered (PDC). The secondary outcome was the percentage of patients who had reached their blood pressure goal at follow-up at 12 months. RESULTS: Patients receiving UI TEAM RX intervention showed significant improvement in mean PDC at 6-month follow-up compared to control patients (P < 0.01). The proportion of patients with a PDC above 0.8 was higher in the intervention group, but this difference was not statistically significant. There was also a 16.4% increase in the proportion of patients who reached their blood pressure goal in the intervention group, although this increase was not statistically significant. CONCLUSION: The UI TEAM RX program had a statistically significant impact on patients' mean PDCs. An increase in the number of patients reaching their blood pressure goal was also seen.
Subject(s)
Hypertension , Pharmaceutical Services , Pharmacy , Humans , Retrospective Studies , Hypertension/diagnosis , Hypertension/drug therapy , Blood PressureABSTRACT
Objective: This systematic review aims to evaluate the impact of psilocybin on patients experiencing psychiatric symptoms, with a focus on health-related quality of life (HRQoL) and safety. Method of Research: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed database and identified studies published from January 2011 to December 2021 pertaining to the impact of psilocybin on psychiatric symptoms. Two authors independently conducted a focused analysis and reached a final consensus on five studies meeting the specific selection criteria. Study bias was addressed using the Cochrane risk of bias tool. Results: The impact of psilocybin on psychiatric symptoms was examined in five randomized controlled trials (RCTs). Four studies administered 1 to 2 doses of psilocybin, with doses ranging from 14mg/70kg to 30mg/70kg, and one study administered a fixed dose of 25mg to all participants. Administration of psilocybin resulted in significant and sustained reduction in symptoms of anxiety and depression, enhanced sense of wellbeing, life satisfaction, and positive mood immediately after psilocybin administration and up to six months after conclusion of treatment. All studies included some form of psychotherapy, and none reported serious adverse effects. Conclusion: RCTs show the efficacy of psilocybin in the treatment of anxiety and depression symptoms, as well as improvement in HRQoL, and no serious side effects. However, additional research is necessary to characterize predictors of treatment response, patient screening requirements, effectiveness in broader clinical populations, and guidelines for psilocybin-assisted psychotherapy.
ABSTRACT
BACKGROUND: Different causes may be responsible for delayed inflammatory reactions after hyaluronic acid injections, among them several mechanisms of SARS-CoV-2. AIMS: The study's objective was to assess the percentage of adverse reactions after hyaluronic acid injections in a cohort of adult patients with a test for SARS-CoV-2 or vaccinated during the COVID-19 pandemic. PATIENTS/METHODS: An observational, retrospective, comparative, multi-center, non-interventional in a real-life setting study was carried out with patients treated with facial injections of hyaluronic acid from May to September 2021, with a test to discard SARS-COV 2 or that had been vaccinated. RESULTS: Sixty-three patients were included. Seven (11.1%) were vaccinated patients without a test for SaRS-CoV-2 and 56 (88.9%) with antigenic or PCR screening tests (18 [32.1%] negative and 39 [69.6%] positives for COVID-19). The mean age was 51.3 (SD 12.71; range 23-70), and 57 (90.5%) were female. Twenty-three patients (36.5%) had a history of adverse events with hyaluronic acid injections. During the study, 15 adverse events were reported; 11 patients (73.3%) had a history (p = 0.0018); two patients (13.3%) had been vaccinated; 13 (86.7%) had performed a SARS-CoV2 test (six [46.2%] negatives, and seven [53.8%] with a positive result; p = 0.5969). All adverse study events were resolved, and none had sequelae. CONCLUSION: Adverse events after hyaluronic acid facial injections were higher among patients with a history but not among those diagnosed with COVID-19. The new scenario related to COVID-19 infections or vaccinations would require readapting criteria for applying hyaluronic acid injections.
Subject(s)
COVID-19 , Humans , Adult , Female , Middle Aged , Male , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Hyaluronic Acid/adverse effects , Retrospective Studies , Pandemics/prevention & control , RNA, ViralABSTRACT
Plants are constantly exposed to a variety of different environmental stresses, including drought, salinity, and elevated temperatures. These stress cues are assumed to intensify in the future driven by the global climate change scenario which we are currently experiencing. These stressors have largely detrimental effects on plant growth and development and, therefore, put global food security in jeopardy. For this reason, it is necessary to expand our understanding of the underlying mechanisms by which plants respond to abiotic stresses. Especially boosting our insight into the ways by which plants balance their growth and their defense programs appear to be of paramount importance, as this may lead to novel perspectives that can pave the way to increase agricultural productivity in a sustainable manner. In this review, our aim was to present a detailed overview of different facets of the crosstalk between the antagonistic plant hormones abscisic acid (ABA) and auxin, two phytohormones that are the main drivers of plant stress responses, on the one hand, and plant growth, on the other.
Subject(s)
Abscisic Acid , Indoleacetic Acids , Plant Growth Regulators , Plants , Stress, Physiological , Signal TransductionABSTRACT
Mutations and aberrant gene expression during cellular differentiation lead to neurodevelopmental disorders, such as Prader-Willi syndrome (PWS), which results from the deletion of an imprinted locus on paternally inherited chromosome 15. We analyzed chromatin-associated RNA in human induced pluripotent cells (iPSCs) upon depletion of hybrid small nucleolar long non-coding RNAs (sno-lncRNAs) and 5' snoRNA capped and polyadenylated long non-coding RNAs (SPA-lncRNAs) transcribed from the locus deleted in PWS. We found that rapid ablation of these lncRNAs affects transcription of specific gene classes. Downregulated genes contribute to neurodevelopment and neuronal maintenance, while upregulated genes are predominantly involved in the negative regulation of cellular metabolism and apoptotic processes. Our data reveal the importance of SPA-lncRNAs and sno-lncRNAs in controlling gene expression in iPSCs and provide a platform for synthetic experimental approaches in PWS studies. We conclude that ncRNAs transcribed from the PWS locus are critical regulators of a transcriptional signature, which is important for neuronal differentiation and development.
Subject(s)
Induced Pluripotent Stem Cells , Prader-Willi Syndrome , RNA, Long Noncoding , Humans , Prader-Willi Syndrome/genetics , Prader-Willi Syndrome/metabolism , Induced Pluripotent Stem Cells/metabolism , RNA, Untranslated , RNA, Small Nucleolar/genetics , RNA, Long Noncoding/genetics , Genomic ImprintingABSTRACT
Dental caries is the major biofilm-mediated oral disease in the world. The main treatment to restore caries lesions consists of the use of adhesive resin composites due to their good properties. However, the progressive degradation of the adhesive in the medium term makes possible the proliferation of cariogenic bacteria allowing secondary caries to emerge. In this study, a dental adhesive incorporating a drug delivery system based on L-arginine-containing mesoporous silica nanoparticles (MSNs) was used to release this essential amino acid as a source of basicity to neutralize the harmful acidic conditions that mediate the development of dental secondary caries. The in vitro and bacterial culture experiments proved that L-arginine was released in a sustained way from MSNs and diffused out from the dental adhesive, effectively contributing to the reduction of the bacterial strains Streptococcus mutans and Lactobacillus casei. Furthermore, the mechanical and bonding properties of the dental adhesive did not change significantly after the incorporation of L-arginine-containing MSNs. These results are yielding glimmers of promise for the cost-effective prevention of secondary caries.
Subject(s)
Dental Caries , Nanoparticles , Humans , Silicon Dioxide , Dental Caries/prevention & control , Arginine , Streptococcus mutans , Dental Cements/pharmacologyABSTRACT
Malate dehydrogenases (MDH) serve a critical role in maintaining equilibrium of the NAD+/NADH ratio between the mitochondria and cytosol through the catalysis of the oxidation of L-malate to oxaloacetate in a reversible, NADH-dependent manner. MDH2 encodes the mitochondrial isoform, which is integral to the tricarboxylic acid cycle and thus energy homeostasis. Recently, five patients harboring compound heterozygous MDH2 variants have been described, three with early-onset epileptic encephalopathy, one with a stroke-like episode, and one with dilated cardiomyopathy. Here, we describe an additional seven patients with biallelic variants in MDH2, the largest and most neurodevelopmentally and ethnically diverse cohort to-date, including homozygous variants, a sibling pair, non-European patients, and an adult. From these patients, we learn that MDH2 deficiency results in a biochemical signature including elevations of plasma lactate and the lactate:pyruvate ratio with urinary excretion of malate. It also results in a recognizable constellation of neuroimaging findings of anterior-predominant cerebral atrophy, subependymal cysts with ventricular septations. We also recognize MDH2 deficiency as a cause of Leigh syndrome. Taken with existing patient reports, we conclude that MDH2 deficiency is an emerging and likely under-recognized cause of infantile epileptic encephalopathy and provide a framework for medical evaluation of patients identified with biallelic MDH2 variants.
ABSTRACT
A superhydrophobic composite coating consisting of polytetrafluoroethylene (PTFE) and poly(acrylic acid)+ ß-cyclodextrin (PAA + ß-CD) was prepared on an aluminum alloy AA 6061T6 substrate by a three-step process of electrospinnig, spin coating, and electrospraying. The electrospinning technique is used for the fabrication of a polymeric binder layer synthesized from PAA + ß-CD. The superhydrophilic characteristic of the electrospun PAA + ß-CD layer makes it suitable for the absorption of an aqueous suspension with PTFE particles in a spin-coating process, obtaining a hydrophobic behavior. Then, the electrospraying of a modified PTFE dispersion forms a layer of distributed PTFE particles, in which a strong bonding of the particles with each other and with the PTFE particles fixed in the PAA + ß-CD fiber matrix results in a remarkable improvement of the particles adhesion to the substrate by different heat treatments. The experimental results corroborate the important role of obtaining hierarchical micro/nano multilevel structures for the optimization of superhydrophobic surfaces, leading to water contact angles above 170°, very low contact angle of hysteresis (CAH = 2°) and roll-off angle (αroll−off < 5°). In addition, a superior corrosion resistance is obtained, generating a barrier to retain the electrolyte infiltration. This study may provide useful insights for a wide range of applications.
ABSTRACT
Autophagy is a highly conserved metabolic pathway via which unwanted intracellular materials, such as unfolded proteins or damaged organelles, are digested. It is activated in response to conditions of oxidative stress or starvation, and is essential for the maintenance of cellular homeostasis and other vital functions, such as differentiation, cell death, and the cell cycle. Therefore, autophagy plays an important role in the initiation and progression of tumors, including hematological malignancies, where damaged autophagy during hematopoiesis can cause malignant transformation and increase cell proliferation. Over the last decade, the importance of autophagy in response to standard pharmacological treatment of hematological tumors has been observed, revealing completely opposite roles depending on the tumor type and stage. Thus, autophagy can promote tumor survival by attenuating the cellular damage caused by drugs and/or stabilizing oncogenic proteins, but can also have an antitumoral effect due to autophagic cell death. Therefore, autophagy-based strategies must depend on the context to create specific and safe combination therapies that could contribute to improved clinical outcomes. In this review, we describe the process of autophagy and its role on hematopoiesis, and we highlight recent research investigating its role as a potential therapeutic target in hematological malignancies. The findings suggest that genetic variants within autophagy-related genes modulate the risk of developing hemopathies, as well as patient survival.