Biomedical applications of MnO2 nanomaterials as nanozyme-based theranostics.

Manganese dioxide (MnO2) nanoenzymes/nanozymes (MnO2-NEs) are 1-100 nm nanomaterials that mimic catalytic, oxidative, peroxidase, and superoxide dismutase activities. The oxidative-like activity of MnO2-NEs makes them suitable for developing effective and low-cost colorimetric detection assays of biomolecules. Interestingly, MnO2-NEs also demonstrate scavenging properties against reactive oxygen species (ROS) in various pathological conditions. In addition, due to the decomposition of MnO2-NEs in the tumor microenvironment (TME) and the production of Mn2+, they can act as a contrast agent for improving clinical imaging diagnostics. MnO2-NEs also can use as an in situ oxygen production system in TME, thereby overcoming hypoxic conditions and their consequences in the progression of cancer. Furthermore, MnO2-NEs as a shell and coating make the nanosystems smart and, therefore, in combination with other nanomaterials, the MnO2-NEs can be used as an intelligent nanocarrier for delivering drugs, photosensitizers, and sonosensitizers in vivo. Moreover, these capabilities make MnO2-NEs a promising candidate for the detection and treatment of different human diseases such as cancer, metabolic, infectious, and inflammatory pathological conditions. MnO2-NEs also have ROS-scavenging and anti-bacterial properties against Gram-positive and Gram-negative bacterial strains, which make them suitable for wound healing applications. Given the importance of nanomaterials and their potential applications in biomedicine, this review aimed to discuss the biochemical properties and the theranostic roles of MnO2-NEs and recent advances in their use in colorimetric detection assays of biomolecules, diagnostic imaging, drug delivery, and combinatorial therapy applications. Finally, the challenges of MnO2-NEs applications in biomedicine will be discussed.

Investigation of the role of prolines 232/233 in RTPPK motif in tau protein aggregation: An in vitro study.

Disease-related tau protein in Alzheimer's disease is hyperphosphorylated and aggregates into neurofibrillary tangles. The cis-proline isomer of the pSer/Thr-Pro sequence has been proposed to act as a precursor of aggregation ('Cistauosis' hypothesis), but this aggregation scheme is not yet entirely accepted. Hence to investigate isomer-specific-aggregation of tau, proline residues at the RTPPK motif were replaced by alanine residues (with permanent trans configuration) employing genetic engineering methods. RTPAK, RTAPK, and RTAAK mutant variants of tau were generated, and their in vitro aggregation propensity was investigated using multi-spectroscopic techniques. Besides, the cell toxicity of oligomers/fibrils was analyzed and compared to those of the wild-type (WT) tau. Analyses of mutant variants have shown to be in agreement (to some degree) to the theory of the 'cistauosis' hypothesis. The results showed that the trans isomer in the 232-rd residue (P232A mutant rather than P233A) had reduced aggregation propensity. However, this study did not illustrate any statistically significant difference between the wild and the mutant protein aggregations concerning cell toxicity.

Phenylalanine gold nanoclusters as sensing platform for π-π interfering molecules: a case study of iodide.

The photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π-π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.

New Insights into the Biosensing of Parkinson's Disease Biomarkers: A Concise Review.

BACKGROUND: Parkinson's disease (PD) is a long-term, degenerative, and neurological disease in which a person loses control of certain body functions. The formulation of novel effective therapeutics for PD as a neurodegenerative disease requires accurate and efficient diagnosis at the early stages. OBJECTIVE: Analyzing data gathered by measurable signals converted from biological reactions allows for qualitative and quantitative evaluations. Among various approaches reported so far, biosensors are powerful analytical tools that have been used in detecting the biomarkers of PD. METHODS: Biosensor's biological recognition components include antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, and biomimetic structures. This review introduces electrochemical, optical, and optochemical detection of PD biomarkers based on recent advances in nanotechnology and material science, which resulted in the development of high-performance biosensors in this field. RESULTS: PD biomarkers such as α-synuclein protein, dopamine (DA), urate, ascorbic acid, miRNAs, and their biological roles are summarized. Additionally, the advantages and disadvantages of the usual standard methods are reviewed. We compared electrochemical, optical, and optochemical biosensors' properties and novel strategies for higher sensitivity and selectivity. CONCLUSION: The development of novel biosensors is required for the early diagnosis of PD as sensitive, rapid, reliable, and cost-effective systems.

Nano-organic supports for enzyme immobilization: Scopes and perspectives.

A variety of organic nanomaterials and organic polymers are used for enzyme immobilization to increase enzymes stability and reusability. In this study, the effects of the immobilization of enzymes on organic and organic-inorganic hybrid nano-supports are compared. Immobilization of enzymes on organic support nanomaterials was reported to significantly improve thermal, pH and storage stability, acting also as a protection against metal ions inhibitory effects. In particular, the effects of enzyme immobilization on reusability, physical, kinetic and thermodynamic parameters were considered. Due to their biocompatibility with low health risks, organic support nanomaterials represent a good choice for the immobilization of enzymes. Organic nanomaterials, and especially organic-inorganic hybrids, can significantly improve the kinetic and thermodynamic parameters of immobilized enzymes compared to macroscopic supports. Moreover, organic nanomaterials are more environment friendly for medical applications, such as prodrug carriers and biosensors. Overall, organic hybrid nanomaterials are receiving increasing attention as novel nano-supports for enzyme immobilization and will be used extensively.

Chemometric modeling of the electrochemical data to investigate proline cis/trans isomeration effect on aggregation of Tau protein.

Tau protein (Tau) is a proline-rich protein and in this work, we have developed a very interesting strategy based on combination of electrochemistry with chemometric methods to investigate proline cis/trans isomeration effect on the Tau aggregation. To achieve this goal, the proline residues at RTPPK motif have been replaced by alanine to generate RTPAK, RTAPK and RTAAK mutants of the Tau. Then, cyclic voltammetric (CV) responses of the Tau and RTPAK, RTAPK and RTAAK as its mutants in the presence of heparin (HEP) as an anionic inducing agent which could trigger aggregation of the Tau were recorded at physiological conditions every hour during 12 h. Therefore, 48 data sets of titrations were obtained which were handled by chemometric methods to extract useful information about aggregation of the Tau. The data were hard-modeled by EQUISPEC, SQUAD, REACTLAB and SPECFIT to extract useful quantitative information. Our results confirmed that the strength of the binding of the HEP with proteins was obeyed from Tau > RTPAK ~ RTAPK > RTAAK which confirmed that the aggregation of the proteins was obeyed from this order as well. Therefore, aggregation of the Tau is decreased by transforming Cis isomer to Trans even in the presence of an anionic inducing agent such as HEP which may have value for the treatment of Alzheimer's disease.

Transient transfection of WT-αS and A53T-αS brought about a mild apoptosis due to degradation of released cytochrome c through PARC.

α-Synuclein (αS) aggregates plays a pivotal role in the pathogenesis of synucleinopathies including Parkinson's Disease. The toxicity of αS aggregates has been broadly studied and variant defects have been reported through which these aggregates lead in cell death. Although cell death through apoptosis pathway has been proposed in many studies, the molecular details underlying in this pathway have not been uncovered. To shed a light on the relationships between αS aggregates and apoptotic cell death, changes in levels and behavior of molecular indicators of the intrinsic apoptotic pathway was investigated in HEK-293T cells overexpressing wild-type α-synuclein and A53T-α-synuclein. Overexpression of both WT-αS and A53T-αS resulted in the increase of caspase-9 activity, and rise in Cytochrome c (Cyt c) and PARC content, concurrently. We assume that rising in PARC level may result in Cyt c degradation, and consequently suppressing/attenuating intrinsic apoptosis pathway. Besides, increasing of Casp-9 activity can be related to αS aggregates and subsequent degradation of Cyt c. To understand the mechanisms behind this using theoretical model, molecular dynamic simulation was also applied to investigate the possible interaction of Casp-9 with α-synuclein aggregates. The results showed that the interaction between Casp-9 with αS aggregates could activate Casp-9 by changing the conformation of some crucial residues.

Biocompatibility assessments of 316L stainless steel substrates coated by Fe-based bulk metallic glass through electro-spark deposition method.

Metallic materials made of rather precious alloys are widely used in orthopedic surgery, circulatory system, and dentistry fields. Stainless steel coated by alloys with a variety of physiochemical properties can be an excellent candidate for making economical devices with superior biomedical compatibility. In this study, a Fe- based metallic glass alloy was applied on 316L stainless steel (316L SS) using the electro-spark deposition (ESD) method as an economic and easy handling method. The coated samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and atomic force microscopy (AFM). It was found that a metallic glass coating was uniformly formed on the stainless steel substrate. Cytocompatibility (MTT assay), hemocompatibility, and cell attachment assays of the fabricated biomaterials were carried out using bone and connective tissue cell lines. The samples with optimized coating were shown to exert lower cytotoxicity, better cell attachment, and higher blood compatibility than the stainless steel substrates.

Sunset yellow degradation product, as an efficient water-soluble inducer, accelerates 1N4R Tau amyloid oligomerization: In vitro preliminary evidence against the food colorant safety in terms of "Triggered Amyloid Aggregation".

Today, Alzheimer's disease (AD) as the most prevalent type of dementia turns into one of the most severe health problems. Neurofibrillary tangle (NFT), mostly comprised of fibrils formed by Tau, is a hallmark of a class of neurodegenerative diseases. Tau protein promotes assembly and makes stable microtubules that play a role in the appropriate function of neurons. Polyanionic cofactors such as heparin, and azo dyes, can induce aggregation of tau protein in vitro. Sunset Yellow is a food colorant used widely in food industries. In the current work, we introduced degradation product (DP) of Sunset Yellow as an effective inducer of Tau aggregation. Two Tau aggregation inducers were produced, and then the aggregation kinetics and the structure of 1N4R Tau amyloid fibrils were characterized using ThT fluorescence spectroscopy, X-Ray Diffraction (XRD), circular dichroism (CD) and atomic force microscopy (AFM). Also, the toxic effects of the induced aggregates on RBCs and SH-SY5Y cells were demonstrated by hemolysis and LDH assays, respectively. Both inducers efficiently accelerated the formation of the amyloid fibril. Along with the confirmation of the ß-sheets structure in Tau aggregates by Far-UV CD spectra, X-ray diffractions revealed the typical cross-ß diffraction pattern. The oligomer formation in the presence of DPs was also confirmed by AFM. The possible in vivo effect of artificial azo dyes on Tau aggregation should be considered seriously as a newly opened dimension in food safety and human health.

Biosensors for detection of Tau protein as an Alzheimer's disease marker.

Known as a main neural MAP (microtubule associated protein), tau protein contributes to stabilizing microtubules involved in cellular transmission. Tau dysfunction is mainly associated with neurodegenerative diseases, particularly Alzheimer's disease (AD). In these patients, all the six tau isoforms, which are in hyperphosphorylated form, are first aggregated and then polymerized into neurofibrillary tangles inside the brain. Tau protein detected in cerebrospinal fluid (CSF) is significantly correlated with AD and is well recognized as a hallmark of the disease. Served for detection of analytes of interest, biosensor device comprises a physical transducer and a keen biological recognition component. Qualitative and quantitative evaluations may be performed through analyzation of the data, which is gathered by measurable signals converted from biological reaction. Antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, as well as some biomimetic structures, normally constitute the biosensor biological recognition part. Production of nanobiosensor, which was made possible through several accomplishments in nano- and fabrication technology, opens up new biotechnological horizons in diagnosis of multiple diseases. In recent years, many researches have been focused on developing novel and effective tau protein biosensors for rapid and accurate detection of AD. In this review, tau protein function and correlation with AD as well as the eminent research on developing nanobiosensor based on optical, electrochemical and piezoelectric approaches will be highlighted.

Improvement in mechanical properties and biodegradability of PLA using poly(ethylene glycol) and triacetin for antibacterial wound dressing applications.

Wound is among the most common injuries. A suitable wound dressing has a significant effect on the healing process. In this study, a porous wound dressing was prepared using poly (lactic acid) (PLA) and two plasticizers, polyethylene glycol (PEG) and triacetin (TA), through solvent casting method. For antibacterial activities, metronidazole was incorporated in the structure. The morphology was investigated by scanning electron microscopy (SEM). In addition, the effect of plasticizers ratio on porosity growth was evaluated. It was also observed that each had a unique effect on the structure's porosity. The mechanical properties confirmed the effect of both plasticizers on increasing polymer softness and flexibility, and the most similar formulations to human skin in terms of mechanical properties were introduced. According to the results, TA had stronger effect on mechanical properties. The differential scanning calorimetry (DSC) showed the effect of increasing plasticizer concentration on crystalline structure and Tm reduction of PLA. The water contact angle measurement showed that both plasticizers enhanced hydrophilic characteristics of PLA, and this effect was weaker in PEG-containing formulations. The in vitro degradation study showed biodegradability, as a desirable property in wound dressing. Results suggested that higher degradation can be obtained by both plasticizers at the same time. The results also showed that PEG was more effective in enhancing water absorbency. In vitro drug release study indicated an explosive release and the highest amount was 85% over 186 h. The antibacterial activity test confirmed the effectiveness of the drug in preventing bacterial growth in the drug-containing formulations, while it showed the antibacterial property of TA. MTT assay was performed and the cellular toxicity of the formulations was checked and those that revealed the least toxicity were introduced.

Sustainable drug release from highly porous and architecturally engineered composite scaffolds prepared by 3D printing.

Additive manufacturing techniques have evolved novel opportunities for the fabrication of highly porous composite scaffolds with well-controlled and interconnected pore structures which is notably important for tissue engineering. In this work, poly (ε-caprolactone) (PCL)-based composite scaffolds (average pore diameter of 450 µm and strut thickness of 400 µm) reinforced with 10 vol% bioactive glass particles (BG; ∼6 µm) or TiO2 nanoparticles (∼21 nm), containing different concentrations of tetracycline hydrochloride (TCH) as an antimicrobial agent, were prepared by 3D printing. In order to investigate the effect of fabrication process and scaffold geometry on the biocompatibility, drug release kinetics, and antibacterial activity, polymer and composite films (2D structures) were also prepared by solvent casting method. We demonstrate that even without any additional coating layer, sustainable release can be attained on highly porous scaffolds prepared by 3D printing due to chemical interactions between functional groups of TCH and the bioactive particles. Herein, the effect of TiO2 nanoparticles on the release rate is substantially more pronounced than BG particles. Nevertheless, agar well-diffusion and MTT assays determine better cellular viability and higher antibacterial effect for PCL/BG composite. Although all the drug-eluting composite scaffolds exhibit acceptable hemocompatibility, in vitro cellular and bacterial studies also determine that the maximum amount of TCH that can inhibit gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria without cytotoxicity effect (≥95% viability) is 0.57 mg/ml. These findings may pave the way for designing structurally engineered composite scaffolds with sustainable drug release profile by additive manufacturing techniques for tissue engineering applications.

Facile Method for Morphological Characterization at Nano Scale.

BACKGROUND: Dynamic light scattering (DLS) and electron microscopy (EM) are the most practical techniques for nanoparticles (NPs) characterization. However, the impediments which involved the sample preparation method lead to failure in provided results of mentioned device analysis. These problems will be intensifying, if the examined samples are the soft nanocarriers such as organic ones or biological samples. OBJECTIVES: In order to achieve the appropriate results from DLS and EM analysis, an optimized protocol was introduced by this research which would prepare samples with high degree of quality and accuracy. MATERIALS AND METHODS: Morphological analysis of prepared polymeric nanocarriers (micelles, nanogels) by this protocol were done. Filtration, dilution and sonication as three crucial and effectiveness steps of sample preparation were assessed through DLS data and EM images. RESULTS: This research has tried to introduce a facile method with novelty of simplicity and rapidity. These triple steps could improve the quality of morphological data. The obtained results indicated that sample preparation methods have the most effective factors on sample size distribution and homogeneity of desired samples. CONCLUSION: The suggested optimized preparation method will be helpful for all soft nanomaterial's samples.

Electrochemical-Based Biosensors: New Diagnosis Platforms for Cardiovascular Disease.

One of the major reasons for mortality throughout the world is cardiovascular diseases. Therefore, bio-markers of cardiovascular disease are of high importance to diagnose and manage procedure. Detecting biomarkers provided a promising procedure in developing bio-sensors. Fast, selective, portable, accurate, inexpensive, and sensitive biomarker sensing instruments will be necessary for detecting and predicting diseases. One of the cardiac biomarkers may be ordered as C-reactive proteins, lipoprotein-linked phospho-lipase, troponin I or T, myoglobin, interleukin-6, interleukin-1, tumor necrosis factor alpha, LDL and myeloperoxidase. The biomarkers are applied to anticipate cardio-vascular illnesses. Initial diagnoses of these diseases are possible by several techniques; however, they are laborious and need costly apparatus. Current researches designed various bio-sensors for resolving the respective issues. Electrochemical instruments and the proposed bio-sensors are preferred over other methods due to its inexpensiveness, mobility, reliability, repeatability. The present review comprehensively dealt with detecting biomarkers of cardiovascular disease through electro-chemical techniques.

Exosomes and cancer: From oncogenic roles to therapeutic applications.

Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell-to-cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this regard, we have given a brief overview of challenges and obstacles in using exosomes as therapeutic agents.

The antidepressant drug; trazodone inhibits Tau amyloidogenesis: Prospects for prophylaxis and treatment of AD.

Tau protein, characterized as "natively unfolded", is involved in microtubule assembly/stabilization in physiological conditions. Under pathological conditions, Tau dysfunction leads to its accumulation of insoluble toxic amyloid aggregates and thought to be involved in the degeneration and neuronal death associated with neurodegenerative diseases. Trazodone (TRZ), a triazolopyridine derivative, is a selective serotonin reuptake inhibitor (SSRI) which increases serotonin levels in synaptic cleft and potentiating serotonin activity, with antidepressant and sedative properties. This drug is more effective and tolerable than other therapeutic agents. In this study, the 1N4R isoform of Tau protein was purified and the effect of TRZ on the protein fibrillation was investigated using multi-spectroscopic techniques as well as computational methods. The results showed that TRZ is not only able to affect formation of Tau amyloid fibrils in vitro but also attenuates Tau oligomerization within SH-SY5Y cell line resulting in more cells surviving. Moreover, membrane disrupting activity of Tau aggregates decreased upon TRZ treatment. The binding forces involved in TRZ-Tau interaction were also explored using both experimental as well as theoretical docking/molecular dynamics approaches. The results of the current work may open new insights for applying therapeutic potential of TRZ against Alzheimer's disease.

Long Non-Coding RNAs As Epigenetic Regulators in Cancer.

Long noncoding RNAs (lncRNAs) constitute large portions of the mammalian transcriptome which appeared as a fundamental player, regulating various cellular mechanisms. LncRNAs do not encode proteins, have mRNA-like transcripts and frequently processed similar to the mRNAs. Many investigations have determined that lncRNAs interact with DNA, RNA molecules or proteins and play a significant regulatory function in several biological processes, such as genomic imprinting, epigenetic regulation, cell cycle regulation, apoptosis, and differentiation. LncRNAs can modulate gene expression on three levels: chromatin remodeling, transcription, and post-transcriptional processing. The majority of the identified lncRNAs seem to be transcribed by the RNA polymerase II. Recent evidence has illustrated that dysregulation of lncRNAs can lead to many human diseases, in particular, cancer. The aberrant expression of lncRNAs in malignancies contributes to the dysregulation of proliferation and differentiation process. Consequently, lncRNAs can be useful to the diagnosis, treatment, and prognosis, and have been characterized as potential cancer markers as well. In this review, we highlighted the role and molecular mechanisms of lncRNAs and their correlation with some of the cancers.

Auditing the appropriateness of cesarean delivery using the Robson classification among women experiencing a maternal near miss.

OBJECTIVE: To evaluate appropriateness of cesarean delivery and cesarean delivery-related morbidity among maternal near misses (MNMs) using the Robson ten-group classification system. METHODS: In the present audit study, medical records were assessed for women who experienced MNM and underwent cesarean delivery at three university hospitals in Tehran, Iran, between March 1, 2012, and May 1, 2014. Local auditors assessed cesarean delivery indications and morbidity experienced. All records were re-assessed using Swedish obstetric guidelines. Findings were reported using the Robson ten-group classification system. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Of the 61 women included, cesarean deliveries were more likely to be considered appropriate by local auditors compared with Swedish ones (OR 2.7, 95% CI 1.3-5.7). Cesarean delivery-related morbidity was attributed to near-miss events for 10 (16%) MNMs and was found to have aggravated 25 (41%). Of 16 women classified as Robson group 1-4, cesarean delivery-related MNM was identified in 15 (94%), compared with 13 (43%) of 30 women in group 10. Cesarean delivery with appropriate indication was associated with very low likelihood of cesarean delivery-related MNM (OR 0.2, 95% CI 0.1-0.6). CONCLUSION: Cesarean delivery in the absence of appropriate indication could be an unsafe delivery choice. Audits using the Robson classification system facilitate understanding inappropriate cesarean delivery and its impact on maternal health.

Preparation of liposomal doxorubicin-graphene nanosheet and evaluation of its in vitro anti-cancer effects.

In recent years there has been much interest in development of multifunctional drug delivery systems. In this work, liposomes that contain doxorubicin (Dox), a potent anticancer drug, and graphene nanosheets (GNS) were prepared. The GNSs have excellent optical properties, such as photoluminescence which enables tracking of the liposomes, high absorption in ultra violet region of electromagnetic spectrum which can be exploited in photodynamic and photothermal therapy, and low toxicity to mammalian cells. Nanoliposomes were prepared using the thin film hydration method. Dox and GNSs were loaded to the liposomes during the hydration of the lipid film. Liposomes were characterized and the profile of in vitro drug release, cellular uptake, and cytotoxicity of the prepared liposomes on MCF-7 cells were determined. Despite the earlier reports, the liposomes have kept their spherical structures in the presence of GNSs. The cytotoxicity of liposomal Dox and GNSs were shown to be higher than the free forms of them. Novel nanoliposomes that contain GNSs have provided a multi-functional system with the potential of tracking, photodynamic and photothermal therapy. Further improvements of this versatile nanosystem would be promising for treatment of cancer.

The effect of auriculotherapy on the severity and duration of labor pain.

INTRODUCTION: Pain is a common phenomenon and an inevitable part of the labor process. Labor pain is one of the most severe pains. Auriculotherapy is one of the nonpharmacological aspects of relieving pain, reduces the intensity of pain, and improves its compatibility. The purpose of this study was to determine the effect of auriculotherapy on labor pain in primiparous women. MATERIALS AND METHODS: This clinical trial was performed on 84 pregnant women aged between 18 and 35 years, who referred to Isfahan Shahid Beheshti Hospital in 2017. This study was carried out between two groups: control group (receiving routine hospital care) and interventional group (20 min for auriculotherapy). We used the McGill Short-Form Standard questionnaire with Visual Analog Scale. Data were analyzed by SPSS software using paired t-test and ANOVA. RESULTS: The results showed that there was no significant difference between demographic variables in the two groups. Statistical analysis also showed that the severity of labor pain in the interventional group (auriculotherapy) was lower than that of the control group (P = 0.001). CONCLUSION: Auriculotherapy reduces the severity of labor pain in primiparous women. Due to the easy, inexpensive, and noninvasive nature of this method, its use has been recommended in these cases.