Effect of Pharmaceutical Intervention in Pharmacologically Treated Hypertensive Patients-A Cluster-Randomized Clinical Trial: AFPRES-CLM Study.

BACKGROUND: Evaluate the effect of a community pharmaceutical intervention on the control of blood pressure in hypertensive patients treated pharmacologically. METHODS: A cluster-randomized clinical trial of 6 months was carried out. It was conducted in the Autonomous Community of Castilla-La Mancha (Spain). Sixty-three community pharmacies and 347 patients completed the study. Intervention patients received the community pharmaceutical intervention based on a protocol that addresses the individual needs of each patient related to the control of their blood pressure, which included Health Education, Pharmacotherapy Follow-up and 24 h Ambulatory Blood Pressure Measurement. Control patients received usual care in the community pharmacy. RESULTS: The pharmaceutical intervention resulted in better control of blood pressure (85.8% vs. 66.3% p < 0.001), lower use of emergencies (p = 0.002) and improvement trends in the physical components of quality of life, measured by SF-36 questionnaire, after 6 months of pharmaceutical intervention. No significant changes were observed for any of these variables in the control group. There were also detected 354 negative medication-related outcomes that were satisfactorily resolved in a 74.9% of the cases and 330 healthcare education interventions and 29 Ambulatory Blood Pressure Monitorings were performed in order to increase adherence to pharmacological treatment and minimize Negative Outcomes associated with Medication and prevent medication-related problems. CONCLUSIONS: Community pharmaceutical intervention can increase hypertensive patients with controlled blood pressure, after 6 months, compared with usual care.

Dopamine D3 Receptor Modulates Akt/mTOR and ERK1/2 Pathways Differently during the Reinstatement of Cocaine-Seeking Behavior Induced by Psychological versus Physiological Stress.

Stress triggers relapses in cocaine use that engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and dentate gyrus (DG). Preclinical research suggests that D3 receptor (D3R) antagonists may be a promising means to attenuate cocaine reward and relapse. As D3R regulates the activity of the Akt/mTOR and MEK/ERK1/2 pathways, we assessed the effects of SB-277011-A, a D3R antagonist, on the activity of these kinases during the reinstatement of cocaine-induced conditioned place preference (CPP) induced by psychological (restraint) and physiological (tail pinch) stress. Both stimuli reactivated an extinguished cocaine-CPP, but only restrained animals decreased their locomotor activity during reinstatement. Cocaine-seeking behavior reactivation was correlated with decreased p-Akt, p-mTOR, and p-ERK1/2 activation in both nuclei of restrained animals. While a D3R blockade prevented stress-induced CPP reinstatement and plasma corticosterone enhancement, SB-277011-A distinctly modulated Akt, mTOR, and ERK1/2 activation depending on the stressor and the dose used. Our data support the involvement of corticosterone in the SB-277011-A effects in restrained animals. Additionally, the ratios p-mTOR/mTOR and/or p-ERK1/2 /ERK1/2 in the BLA during stress-induced relapse seem to be related to the locomotor activity of animals receiving 48 mg/kg of the antagonist. Hence, our study indicates the D3R antagonist's efficacy to prevent stress-induced relapses in drug use through distinct modulation of Akt/mTOR and MEK/ERK1/2 pathways in memory-processing nuclei.

Morphine-withdrawal aversive memories and their extinction modulate H4K5 acetylation and Brd4 activation in the rat hippocampus and basolateral amygdala.

Chromatin modification is a crucial mechanism in several important phenomena in the brain, including drug addiction. Persistence of drug craving and risk of relapse could be attributed to drug-induced epigenetic mechanisms that seem to be candidates explaining long-lasting drug-induced behaviour and molecular alterations. Histone acetylation has been proposed to regulate drug-seeking behaviours and the extinction of rewarding memory of drug taking. In this work, we studied the epigenetic regulation during conditioned place aversion and after extinction of aversive memory of opiate withdrawal. Through immunofluorescence assays, we assessed some epigenetic marks (H4K5ac and p-Brd4) in crucial areas related to memory retrieval -basolateral amygdala (BLA) and hippocampus-. Additionally, to test the degree of transcriptional activation, we evaluated the immediate early genes (IEGs) response (Arc, Bdnf, Creb, Egr-1, Fos and Nfkb) and Smarcc1 (chromatin remodeler) through RT-qPCR in these nuclei. Our results showed increased p-Brd4 and H4K5ac levels during aversive memory retrieval, suggesting a more open chromatin state. However, transcriptional activation of these IEGs was not found, therefore suggesting that other secondary response may already be happening. Additionally, Smarcc1 levels were reduced due to morphine chronic administration in BLA and dentate gyrus. The activation markers returned to control levels after the retrieval of aversive memories, revealing a more repressed chromatin state. Taken together, our results show a major role of the tandem H4K5ac/p-Brd4 during the retrieval of aversive memories. These results might be useful to elucidate new molecular targets to improve and develop pharmacological treatments to address addiction and to avoid drug relapse.

Preclinical safety and efficacy of lentiviral-mediated gene therapy for leukocyte adhesion deficiency type I.

Leukocyte adhesion deficiency type I (LAD-I) is a primary immunodeficiency caused by mutations in the ITGB2 gene, which encodes for the CD18 subunit of ß2-integrins. Deficient expression of ß2-integrins results in impaired neutrophil migration in response to bacterial and fungal infections. Using a lentiviral vector (LV) that mediates a preferential myeloid expression of human CD18 (Chim.hCD18-LV), we first demonstrated that gene therapy efficiently corrected the phenotype of mice with severe LAD-I. Next, we investigated if the ectopic hCD18 expression modified the phenotypic characteristics of human healthy donor hematopoietic stem cells and their progeny. Significantly, transduction of healthy CD34+ cells with the Chim.hCD18-LV did not modify the membrane expression of CD18 nor the adhesion of physiological ligands to transduced cells. Additionally, we observed that the repopulating properties of healthy CD34+ cells were preserved following transduction with the Chim.hCD18-LV, and that a safe polyclonal repopulation pattern was observed in transplanted immunodeficient NOD scid gamma (NSG) mice. In a final set of experiments, we demonstrated that transduction of CD34+ cells from a severe LAD-I patient with the Chim.hCD18-LV restores the expression of ß2-integrins in these cells. These results offer additional preclinical safety and efficacy evidence supporting the gene therapy of patients with severe LAD-I.

Variables psicológicas implicadas en el abuso o consumo indebido de opioides en pacientes con dolor crónico no oncológico / Psychological variables involved in opioid abuse or misuse in patients with chronic non-cancer pain

Las variables psicológicas permiten predecir el riego de abuso de los opioidesde prescripción. El objetivo del presente estudio ha sido analizar el valor predictivode algunas de ellas. Concretamente se ha analizado la asociación del humor deautoafirmación, el neuroticismo, la extraversión, la presencia de síntomas deansiedad y/o depresión, y la intensidad de dolor percibido con el potencial abuso yel uso indebido de opioides. Participaron 60 pacientes con dolor crónico nooncológico, con una media de edad de 60 años, en su mayoría mujeres (77%) ycasados (78%). Se realizaron dos análisis de regresión lineal múltiple por pasos. Losresultados señalan a los síntomas de ansiedad y/o depresión como únicas variablesrelacionadas con el potencial abuso y el actual uso indebido de los opioides deprescripción. Se concluye la importancia de llevar a cabo una evaluación psicológicaprevia al inicio de una terapia farmacológica con opioides. Y, en el caso de detectarsíntomas de ansiedad o depresión en estos pacientes, sería necesario solucionarestos problemas antes de la prescripción de opioides. (AU)

Psychological variables can be used to predict the risk of prescription opioidabuse. The aim of the present study was to analyse the predictive value of a set ofthese variables. Specifically, we analysed the association between the potentialabuse and misuse of opioids and self-affirming mood, neuroticism, extraversion,anxiety and/or depression symptoms, and perceived pain intensity. The samplecomprised 60 patients with chronic non-oncological pain (mean age= 60 years;77% women, 78% married). Two stepwise multiple linear regression analyses wereperformed. The results indicate that anxiety and/or depression symptoms were theonly variables associated with the potential abuse and current misuse ofprescription opioids. We suggest the need for prior psychological assessmentbefore deciding to initiate pharmacological therapy with opioids. Any anxiety or depression symptoms in these patients should be addressed before prescribingopioids. (AU)

Molecular Mechanisms Underlying the Retrieval and Extinction of Morphine Withdrawal-Associated Memories in the Basolateral Amygdala and Dentate Gyrus.

Despite their indisputable efficacy for pain management, opiate prescriptions remain highly controversial partially due to their elevated addictive potential. Relapse in drug use is one of the principal problems for addiction treatment, with drug-associated memories being among its main triggers. Consequently, the extinction of these memories has been proposed as a useful therapeutic tool. Hence, by using the conditioned place aversion (CPA) paradigm in rats, we investigated some of the molecular mechanisms that occurr during the retrieval and extinction of morphine withdrawal memories in the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which control emotional and episodic memories, respectively. The retrieval of aversive memories associated with the abstinence syndrome paralleled with decreased mTOR activity and increased Arc and GluN1 expressions in the DG. Additionally, Arc mRNA levels in this nucleus very strongly correlated with the CPA score exhibited by the opiate-treated rats. On the other hand, despite the unaltered mTOR phosphorylation, Arc levels augmented in the BLA. After the extinction test, Arc and GluN1 expressions were raised in both the DG and BLA of the control and morphine-treated animals. Remarkably, Homer1 expression in both areas correlated almost perfectly with the extinction showed by morphine-dependent animals. Moreover, Arc expression in the DG correlated strongly with the extinction of the CPA manifested by the group treated with the opiate. Finally, our results support the coordinated activity of some of these neuroplastic proteins for the extinction of morphine withdrawal memories in a regional-dependent manner. Present data provide evidence of differential expression and activity of synaptic molecules during the retrieval and extinction of aversive memories of opiate withdrawal in the amygdalar and hippocampal regions that will likely permit the development of therapeutic strategies able to minimize relapses induced by morphine withdrawal-associated aversive memories.

Management of an Unusual Metastasis of Cervical Cancer in the Adrenal Bed With Stereotactic Ablative Body Radiation Therapy.

Uterine cervical carcinoma is an important type of cancer among Ecuadorian women, especially in adult women. Survival rates have improved with the development of radiotherapy, surgical techniques, and chemotherapy. However, recurrence and/or metastasis are not unusual phenomena. Frequent sites of metastasis are the lungs, regional lymph nodes, and bones. Atypical locations can also occur on solid organs, such as adrenal glands. Treatment for the rare complication that is adrenal metastasis is individualized, it can include surgical resection, chemotherapy, local ablation, or different types of radiotherapy. We aimed to report a case of an Ecuadorian woman from Quito city with a diagnosis of cervical carcinoma diagnosed in 2009, treated surgically and with adjuvant chemotherapy. Her progression was monitored with medical controls with no recurrence until 2018, when she relapsed with a metastatic invasion of the pelvic ganglia and the surroundings of the abdominal aorta, with a histopathologic diagnosis of adenocarcinoma. She was then treated with chemotherapy and radiotherapy until June 2019. In 2020, she went through a splenectomy and left adrenalectomy to treat vascular thrombosis. In 2021, 37 x 15 mm mass was discovered in the surgical bed of the previously removed adrenal gland. It was treated as an oligometastatic carcinoma with stereotactic body radiotherapy (SBRT) by a linear accelerator.

Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.

Proteomics as a Complementary Technique to Characterize Bladder Cancer.

Bladder cancer (BC) is the most common tumor of the urinary tract and is conventionally classified as either non-muscle invasive or muscle invasive. In addition, histological variants exist, as organized by the WHO-2016 classification. However, innovations in next-generation sequencing have led to molecular classifications of BC. These innovations have also allowed for the tracing of major tumorigenic pathways and, therefore, are positioned as strong supporters of precision medicine. In parallel, immunohistochemistry is still the clinical reference to discriminate histological layers and to stage BC. Key contributions have been made to enlarge the panel of protein immunomarkers. Moreover, the analysis of proteins in liquid biopsy has also provided potential markers. Notwithstanding, their clinical adoption is still low, with very few approved tests. In this context, mass spectrometry-based proteomics has remained a step behind; hence, we aimed to develop them in the community. Herein, the authors introduce the epidemiology and the conventional classifications to review the molecular classification of BC, highlighting the contributions of proteomics. Then, the advances in mass spectrometry techniques focusing on maintaining the integrity of the biological structures are presented, a milestone for the emergence of histoproteomics. Within this field, the review then discusses selected proteins for the comprehension of the pathophysiological mechanisms of BC. Finally, because there is still insufficient knowledge, this review considers proteomics as an important source for the development of BC therapies.

Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS.

Because cystoscopy is expensive and invasive, a new method of detecting non-invasive muscular bladder cancer (NMIBC) is needed. This study aims to identify potential serum protein markers for NMIBC to improve diagnosis and to find treatment approaches that avoid disease progression to a life-threatening phenotype (muscle-invasive bladder cancer, MIBC). Here, silver nanoparticles (AgNPs, 9.73 ± 1.70 nm) as a scavenging device together with sequential window acquisition of all theoretical mass spectra (SWATH-MS) were used to quantitatively analyze the blood serum protein alterations in two NMIBC subtypes, T1 and Ta, and they were compared to normal samples (HC). NMIBC's analysis of serum samples identified three major groups of proteins, the relative content of which is different from the HC content: proteins implicated in the complement and coagulation cascade pathways and apolipoproteins. In conclusion, many biomarker proteins were identified that merit further examination to validate their useful significance and utility within the clinical management of NMIBC patients.

Blood-based protein biomarkers in bladder urothelial tumors.

Bladder cancer (BC) is the fifth most common cancer with a high prevalence rate. It is classically classified in two groups, namely non-muscle invasive (NMIBC) and muscle invasive (MIBC). NMIBC accounts for 75% of cases and has a better prognosis than MIBC. However, 30-50% of the NMIBC patients will show recurrences throughout their lives, and about 10-20% of them will progress to MIBC, with frequent metastasis and a reduced survival rate. The diagnosis of bladder cancer is confirmed by direct visualization of the tumour and other mucosal abnormalities with endoscopic excision using cystoscopy and transurethral resection of the bladder (TURBT). An adequate TURBT requires complete resection of all visible tumour with appropriate sampling of the bladder to assess the depth of invasion. However, for many years, researchers have attempted to identify and utilise urinary markers for bladder cancer detection. Voided urine cytology has been the mainstay of urine-based diagnosis of bladder cancer since originally described by Papanicolau and Marshall. Nonetheless, urine cytology has several drawbacks, including a poor sensitivity for low-grade/stage tumours, a lack of interobserver consistency and a variable range of readings (e.g., atypical, atypical-suspicious, non-diagnostic). These shortcomings have inspired the search for more sensitive bladder cancer biomarkers. To bring precision medicine to genitourinary oncology, the analysis of the plasma/serum wide genome and proteome offers promising possibilities.

Protein Extraction From FFPE Kidney Tissue Samples: A Review of the Literature and Characterization of Techniques.

Most tissue biopsies from patients in hospital environments are formalin-fixed and paraffin-embedded (FFPE) for long-term storage. This fixation process produces a modification in the proteins called "crosslinks", which improves protein stability necessary for their conservation. Currently, these samples are mainly used in clinical practice for performing immunohistochemical analysis, since these modifications do not suppose a drawback for this technique; however, crosslinks difficult the protein extraction process. Accordingly, these modifications make the development of a good protein extraction protocol necessary. Due to the specific characteristics of each tissue, the same extraction buffers or deparaffinization protocols are not equally effective in all cases. Therefore, it is necessary to obtain a specific protocol for each tissue. The present work aims to establish a deparaffinization and protein extraction protocol from FFPE kidney samples to obtain protein enough of high quality for the subsequent proteomic analysis. Different deparaffination, protocols and protein extraction buffers will be tested in FFPE kidney samples. The optimized conditions will be applied in the identification by LC-MS/MS analysis of proteins extracted from 5, 10, and 15 glomeruli obtained through the microdissection of FFPE renal samples.

Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress.

Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Moreover, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and the activity of the mTOR pathway, which is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced conditioned place preference (CPP) evoked by drug priming and social stress. Reinstatement of cocaine CPP paralleled an increasing trend in D3R and dopamine transporter (DAT) levels in the BLA. Social stress, but not drug-induced reactivation of cocaine memories, was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), which was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitant with cocaine CPP reactivation, a diminution in mTOR phosphorylation (activation) in the BLA and DG occurred, which was inhibited by D3R blockade in both nuclei before the social stress episode and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while supporting a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicate that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli.

SWATH-MS Protocols in Human Diseases.

Identification of molecular biomarkers for human diseases is one of the most important disciplines in translational science as it helps to elucidate their origin and early progression. Thus, it is a key factor in better diagnosis, prognosis, and treatment. Proteomics can help to solve the problem of sample complexity when the most common primary sample specimens were analyzed: organic fluids of easy access. The latest developments in high-throughput and label-free quantitative proteomics (SWATH-MS), together with more advanced liquid chromatography, have enabled the analysis of large sample sets with the sensitivity and depth needed to succeed in this task. In this chapter, we show different sample processing methods (major protein depletion, digestion, etc.) and a micro LC-SWATH-MS protocol to identify/quantify several proteins in different types of samples (serum/plasma, saliva, urine, tears).

How Are Clinicians Treating Children With Sepsis in Emergency Departments in Latin America?: An International Multicenter Survey.

OBJECTIVE: Guidelines adherence in emergency departments (EDs) relies partly on the availability of resources to improve sepsis care and outcomes. Our objective was to assess the management of pediatric septic shock (PSS) in Latin America's EDs and to determine the impact of treatment coordinated by a pediatric emergency specialist (PEMS) versus nonpediatric emergency specialists (NPEMS) on guidelines adherence. METHODS: Prospective, descriptive, and multicenter study using an electronic survey administered to PEMS and NPEMS who treat PSS in EDs in 14 Latin American countries. RESULTS: We distributed 2164 surveys with a response rate of 41.5%, of which 22.5% were PEMS. Overall American College of Critical Care Medicine reported guidelines adherence was as follows: vascular access obtained in 5 minutes, 76%; fluid infusion technique, 60%; administering 40 to 60 mL/kg within 30 minutes, 32%; inotropic infusion by peripheral route, 61%; dopamine or epinephrine in cold shock, 80%; norepinephrine in warm shock, 57%; and antibiotics within 60 minutes, 82%. Between PEMS and NPEMS, the following differences were found: vascular access in 5 minutes, 87.1% versus 72.7% (P < 0.01); fluid infusion technique, 72.3% versus 55.9% (P < 0.01); administering 40 to 60 mL/kg within 30 minutes, 42% versus 29% (P < 0.01); inotropic infusion by peripheral route, 75.7% versus 56.3% (P < 0.01); dopamine or epinephrine in cold shock, 87.1% versus 77.3% (P < 0.05); norepinephrine in warm shock, 67.8% versus 54% (P < 0.01); and antibiotic administration within first 60 minutes, 90.1% versus 79.3% (P < 0.01), respectively. Good adherence criteria were followed by 24%. The main referred barrier for sepsis care was a failure in its recognition, including the lack of triage tools. CONCLUSIONS: In some Latin American countries, there is variability in self-reported adherence to the evidence-based recommendations for the treatment of PSS during the first hour. The coordination by PEMS support greater adherence to these recommendations.

Unraveling the molecular mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages.

Alcohol interferes with foetal development and prenatal alcohol exposure can lead to adverse effects known as foetal alcohol spectrum disorders. We aimed to assess the underlying neurobiological mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages, in discrete brain areas. Pregnant C57BL/6 female mice were exposed to binge alcohol drinking from gestation to weaning. Subsequently, alcohol seeking and taking behaviour were evaluated in male adolescent offspring, as assessed in the two-bottle choice and oral self-administration paradigms. Brain area samples were analysed to quantify AMPAR subunits GluR1/2 and pCREB/CREB expression following alcohol self-administration. We measured the expression of mu and kappa opioid receptors both during acute alcohol withdrawal (assessing anxiety alterations by the EPM test) and following reinstatement in the two-bottle choice paradigm. In addition, alcohol metabolism was analysed by measuring blood alcohol concentrations under an acute dose of 3 g/kg alcohol. Our findings demonstrate that developmental alcohol exposure enhances alcohol intake during adolescence, which is associated with a decrease in the pCREB/CREB ratio in the hippocampus, prefrontal cortex and striatum, while the GluR1/GluR2 ratio showed a decrease in the hippocampus. Moreover, PLAE mice showed behavioural alterations, such as increased anxiety-like responses during acute alcohol withdrawal, and higher BAC levels. No significant changes were identified for mu and kappa opioid receptors mRNA expression. The current study highlights that early alcohol exposed mice increased alcohol consumption during late adolescence. Furthermore, a diminished CREB signalling and glutamatergic neuroplasticity are proposed as underpinning neurobiological mechanisms involved in the sensitivity to alcohol reinforcing properties.

A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors.

A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput "omics" approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumors.