Generic Pathway Research Articles

Molecular mechanisms of the anticancer action of fustin isolated from Cotinus coggygria Scop. in MDA-MB-231 triple-negative breast cancer cell line.

The aim of the present work was to investigate some of the molecular mechanisms and targets of the anticancer action of the bioflavonoid fustin isolated from theheartwood of Cotinus coggygria Scop. in the triple-negative breast cancer cell line MDA-MB-231. For this purpose, we applied fluorescence microscopy analysis to evaluate apoptosis, necrosis, and mitochondrial integrity, wound healing assay to study fustin antimigratory potential and quantitative reverse transcription-polymerase chain reaction to analyze the expression of genes associated with cell cycle control, programmed cell death, metastasis, and epigenetic alterations. A complex network-based bioinformatic analysis was also employed for protein-protein network construction, hub genes identification, and functional enrichment. The results revealed a significant induction of early and late apoptotic and necrotic events, a slight alteration of the mitochondria-related fluorescence, and marked antimotility effect after fustin treatment. Of 34 analyzed genes, seven fustin targets were identified, of which CDKN1A, ATM, and MYC were significantly enriched in pathways such as cell cycle, intrinsic apoptotic signaling pathway in response to DNA damage and generic transcription pathway. Our findings outline some molecular mechanisms of the anticancer action of fustin pointing it out as a potential oncotherapeutic agent and provide directions for future invivo research.

Intercellular friction and motility drive orientational order in cell monolayers

Spatiotemporal patterns in multicellular systems are important to understanding tissue dynamics, for instance, during embryonic development and disease. Here, we use a multiphase field model to study numerically the behavior of a near-confluent monolayer of deformable cells with intercellular friction. Varying friction and cell motility drives a solid-liquid transition, and near the transition boundary, we find the emergence of local nematic order of cell deformation driven by shear-aligning cellular flows. Intercellular friction contributes to the monolayer's viscosity, which significantly increases the spatial correlation in the flow and, concomitantly, the extent of nematic order. We also show that local hexatic and nematic order are tightly coupled and propose a mechanical-geometric model for the colocalization of [Formula: see text] nematic defects and 5-7 disclination pairs, which are the structural defects in the hexatic phase. Such topological defects coincide with regions of high cell-cell overlap, suggesting that they may mediate cellular extrusion from the monolayer, as found experimentally. Our results delineate a mechanical basis for the recent observation of nematic and hexatic order in multicellular collectives in experiments and simulations and pinpoint a generic pathway to couple topological and physical effects in these systems.

Generic Approach to Intrinsic Magnetic Second-Order Topological Insulators via Inverted p-d Orbitals.

The integration of intrinsically magnetic and topologically nontrivial two-dimensional materials holds tantalizing prospects for exotic quantum anomalous Hall insulators and magnetic second-order topological insulators (SOTIs). Compared with their well-studied nonmagnetic counterparts, the pursuit of intrinsic magnetic SOTIs remains limited. In this work, we address this gap by focusing on p-d orbitals inversion, a fundamental but often overlooked phenomena in the construction of topological materials. We begin by developing a theoretical framework to elucidate p-d orbital inversion through a combined density-functional theory calculation and Wannier downfolding. Subsequently we showcase the generality of this concept in realizing ferromagnetism SOTIs by identifying two real materials with distinct lattices: 1T-VS2 monolayer in a hexagonal lattice and CrAs monolayer in a square lattice. We further compare it with other mechanisms requiring spin-orbit coupling and explore the similarities to topological Kondo insulators. Our findings establish a generic pathway toward intrinsic magnetic SOTIs.

Knowledge-based: facilitating access to medicines in Latin America

The World Health Organization (WHO), with the scientific support of the International Pharmaceutical Federation (FIP), guides the development of multisource pharmaceutical products for market authorization using in vivo bioequivalence studies or, where applicable, in vitro biowaiver strategies based on the Biopharmaceutical Classification System (BCS). A review of the regulatory framework guiding generic medicines approval in Latin American countries revealed that less than 50% of regional health authorities offer a generic medicines development pathway utilizing a BCS-based biowaiver strategy. Aligned with the ONE FIP Strategy to facilitate access to medicines, a regional case study was carried out to implement and harmonize BCS-based biowaiver knowledge in Latin American countries. A steering committee involving regional representatives from health authorities, the pharmaceutical industry, and universities were established to coordinate to develop activities. A series of digital engagement events were held in Spanish and English with representatives from Latin America to share knowledge on BCS-based regulatory strategy, promote collaborations, and explore the alignment of biowaiver approval and regulatory pathways among Latin American countries. Feedback from diverse Latin American stakeholders demonstrated inconsistent implementation of bioequivalence testing within the region. However, there is support for a synergistic approach among countries to reduce duplication and increase efficiency in market authorization for generic medicines. This includes alignment with the WHO Prequalification of Medicines program as well as the development of a computational database for the classification of active pharmaceutical ingredients to demonstrate therapeutic interchangeability of immediate-release oral dosage forms according to the BCS. FIP-facilitated digital learning opportunities raised awareness of the BCS-based biowaiver regulatory strategy among Latin American stakeholders. It resulted in a plan to continually strengthen collaborative efforts in the region to harmonize regulations relevant to drug development generics medicines to introduce cost-effective medicines products that benefit public health.

Synthetic polypeptides using a biologic as a reference medicinal product - the European landscape of regulatory approvals.

Recent advances in synthetic drug manufacturing have introduced a new dynamic to the European regulatory system, with chemically synthesized polypeptide products using biological originator products as their reference medicine. Whereas biosimilars are subject to a dedicated regulatory framework in the EU, synthetically produced follow-on products are not eligible for assessment through this pathway, requiring approval via the traditional generic pathway under Article 10 (1), or via the hybrid pathway under Article 10 (3). This review presents an overview of recent developments in the field of synthetic peptides referencing biological originators in the EU. The use of different regulatory procedures can have potential implications for regulatory assessments, clinical practice and pharmacovigilance. As more complex synthetic products referencing recombinant originator products are expected in the coming years, this study promotes more transparency as well as global alignment about regulatory procedures for chemically synthesised products referencing biological originator products to ensure approval of safe and high-quality generics.

Identification and validation of core genes in tumor-educated platelets for human gastrointestinal tumor diagnosis using network-based transcriptomic analysis

Gastrointestinal (GI) tumors have increasing incidence worldwide with their underlying mechanisms still not being fully understood. The use of tumor-educated platelets (TEPs) in liquid biopsy is a newly-emerged blood-based cancer diagnostic method. Herein, we aimed to investigate the genomic changes of TEPs in GI tumor development and their potential functions using network-based meta-analysis combined with bioinformatic methods. We used a total of three eligible RNA-seq datasets, which were integrated using multiple meta-analysis methods on the NetworkAnalyst website, and identified 775 DEGs (differentially expressed genes; 51 up-regulated and 724 down-regulated genes) in GI tumor relative to healthy control (HC) samples. These TEP DEGs were mostly enriched in bone marrow-derived cell types and associated with gene ontology (GO) of “carcinoma” and could affect pathways of “Integrated Cancer Pathway” and “Generic transcription pathway” respectively for highly and lowly expressed DEGs. Combined network-based meta-analysis and protein–protein interaction (PPI) analysis identified cyclin dependent kinase 1 (CDK1) and heat shock protein family A (Hsp70) member 5 (HSPA5) to be the hub genes with the highest degree centrality (DC), being up-regulated and down-regulated in TEPs, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the hub genes were primarily related to cell cycle and division, nucleobase-containing compound and carbohydrate transport, and endoplasmic reticulum unfolded protein response. Additionally, the nomogram model suggested that the two-gene signature owns extraordinary predictive power for GI tumor diagnosis. Further, the two-gene signature was demonstrated to have potential value for metastatic GI tumor diagnosis. The expression levels of CDK1 and HSPA5 in clinical platelet samples were verified to be consistent with the results from bioinformatic analysis. This study identified a two-gene signature encompassing CDK1 and HSPA5 that can be used as a biomarker for GI tumor diagnosis and maybe even cancer-associated thrombosis (CAT)-related prognosis.

Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.

Evolution, Stability, and Applicability of Surfactant Aggregates in Targeted Delivery.

Self-assembly/self-aggregation of surfactant molecules in bulk and the vicinity of a surface has been a topic of interest for decades because of its utilization in numerous modern technical applications. In this article, the results of molecular dynamics simulations are reported to investigate the self-aggregation of sodium dodecyl sulfate (SDS) at an interface of mica and water. SDS molecules starting from lower to higher surface concentrations tend to create distinct aggregated structures in the vicinity of a mica surface. The structural properties, such as density profiles, radial distribution functions, and thermodynamic properties like excess entropy and second virial coefficient, are calculated to address the bits and pieces of the self-aggregation. The change in the free energy for aggregates of varied sizes approaching the surface from the bulk aqueous solution, along with the change in their shapes during the process in terms of change in the radius of gyration and its components, is reported respectively to model a generic pathway for a surfactant-based targeted delivery system.

Malignant pleural effusion: Updates in diagnosis, management and current challenges.

Malignant pleural effusion (MPE) is a common condition which often causes significant symptoms to patients and costs to healthcare systems. Over the past decade, the management of MPE has progressed enormously with large scale, randomised trials answering key questions regarding optimal diagnostic strategies and effective management strategies. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. The future goals for providing improved care for patients lies in changing the treatment paradigm from a generic pathway to personalised care, based on probability of malignancy type and survival. This article reviews the current evidence base, new discoveries and future directions in the diagnosis and management of MPE.

Transformation of Industry Ecosystems in Cities and Regions: A Generic Pathway for Smart and Green Transition

This research paper focuses on pathways towards a digital and green transition. We assess a generic pathway for the transformation of industry ecosystems in cities and regions based on processes of prioritisation, ecosystem identification, and platform-based digital and green transition. We start with problem definition and hypotheses; review related works on transition pathways, such as digital transition, green transition, system innovation, industry ecosystems, and multi-level perspective of transformation; assess the generic pathway with case studies; and conclude with a discussion of findings, outline of conclusions, and policy implications. Overall, the paper investigates pathways, priorities, and methods allowing public authorities and business organisations to master the current industrial transformation of cities and regions introduced by the twin digital and green transitions as an opportunity for radical change of city ecosystems, innovation leapfrogging, and system innovation.

User perspectives on systematic data collection regarding back pain managed in general practice – a qualitative study

BackgroundBack pain is a main driver of disability and the most prevalent reason why people in Demark visit a general practitioner (GP). However, little is known about back pain management in primary care. For new strategies to be sustainable and to accommodate the recommendations for evidence-based practice, patients’ perspectives are paramount to complement clinical expertise and research evidence.This study aimed to identify recommendations for systematic data collection in a nationwide cohort regarding the management of back pain in general practice from the perspectives of GPs and patients.MethodWe applied an adapted exploratory sequential design using focus groups and individual interviews. Seven GPs and ten patients with back pain participated, and four focus groups and seventeen individual interviews were conducted. Data were analyzed using abductive reasoning.ResultsBoth GPs and patients with back pain found that 1) recruitment to a cohort should take place through the GPs, 2) the heterogeneity of patients with back pain and their need for individualized treatment and care should be considered, and 3) data from the cohort should feed into a flowchart or guideline to illustrate a generic patient pathway and visually assist both the patient and GP to obtain an overview and, thus, structure the patient pathway.ConclusionGPs and patients with back pain both considered the nationwide cohort with the overall aim to investigate back pain management as being extremely relevant in relation to improve t the patient pathway. User perspectives should be explored and integrated into health care interventions.

Work-related support in clinical care for patients with a chronic disease: development of an intervention

BackgroundPatients with a chronic disease are more vulnerable in the labor market, and work-related support in clinical care would enhance the timely support greatly needed in each phase of their working life. This paper describes the development of a generic stay-at-work intervention to provide work-related support in clinical care to patients with a chronic disease.MethodsSteps 1–4 of Intervention Mapping (IM) were combined with action research principles. A needs assessment (Step 1) involved the project group formation, a literature review, qualitative studies with healthcare professionals (HCPs; n = 9) and patients (n = 10), consultation with financial staff and testing, and resulted in objectives (Step 2). Guided by methods and applications (Step 3), the intervention was developed, tested and finalized (Step 4).ResultsThe needs assessment revealed the importance of behavioral change in HCPs, including changing attitude, self-efficacy, and social influence. For that purpose, a pathway and training sessions were developed. Testing these unveiled the need for practical tools and intervision. The final intervention comprises a care pathway as part of working routines, including screening, risk stratification, and tailored support. Practical tools, training sessions, and intervision for HCPs were developed.ConclusionsCombining IM with action research principles resulted in a generic stay-at-work intervention in clinical care via behavioral change in HCPs. A generic care pathway, practical tools, training sessions, and intervision were developed. More specific alignment to specific patient groups is possible. To implement the intervention in another hospital, the local context, (financial) resources, and the national legislation should be considered.

Mind the Gap: Understanding Differences Between Sexual and Reproductive Health-Related Legal Frameworks on Paper and in Practice.

IntroductionUNFPA recently developed a composite indicator to assess sexual and reproductive health (SRH)-related laws as part of the Sustainable Development Goals monitoring framework (Indicator 5.6.2). However, there is still little understanding of how best to ensure a supportive SRH-related legal framework can improve SRH outcomes. This research draws on country case studies (Colombia, Malawi, Uruguay, Zambia) to provide more generalizable lessons on the processes by which these laws are translated into practice and their impact on lived realities.MethodsPeer-reviewed and gray literature on laws and policies related to maternity care, contraception, sexuality education, HIV and HPV was reviewed. Key informant interviews were carried out with 8–16 people in each country, including representatives of government, civil society and academia to understand factors affecting implementation of relevant laws and policies. Findings were thematically analyzed by country and contextualized within each country's score on Indicator 5.6.2 and relevant SRH outcome data.FindingsAcross these countries, some common organizational steps help move from laws on paper to impacting people's lives including budget allocation, development of technical guidance, health worker training, population awareness creation and demand generation. It is also important to address sociocultural challenges such as entrenched inequalities, conservative cultural and religious beliefs and the potential existence of customary law. Challenges can be encountered across all these steps and can vary based on the area of SRH: implementation of laws to reduce maternal mortality is generally less controversial than laws around abortion, often making the latter harder to implement. Local specificities in structures, systems and cultures bring opportunities and challenges, highlighting the need for tailored actions.DiscussionA legal framework supportive to SRH is critical, particularly in the face of backlash against sexual and reproductive rights, but alone it is insufficient. Understanding that a generic pathway exists for moving laws into practice is a critical starting point for exploring the specificities of each national context as a way of identifying entry points for action. These findings can be used to inform advocacy and monitoring to help ensure that the potential benefits of supportive SRH-related laws can be realized in these four countries and around the world.

Effects of structure relaxation and surface oxidation on nanoscopic wear behaviors of metallic glass

Both structure relaxation and oxidation of surface layer induced by thermal treatment or friction heat play significant roles in reducing wear of metallic glasses (MGs). To distinguish the effects of structure relaxation and surface oxidation, we prepared Zr-based MGs at different states, i.e., as-cast MG; the annealed MGs under argon atmosphere (referred to as structure-relaxed MG) and oxygen atmosphere (referred to as oxidized MG). Nano-wear tests were carried out by atomic force microscope (AFM) to quantitatively clarify these two effects on the wear performance. Compared with the as-cast MG, the structure-relaxed MG shows an increased adhesive but slightly decreased ploughing friction. While, the oxidized MG shows the best anti-wear performance with dramatic reductions in both adhesive and ploughing friction. Classic molecular dynamics (MD) and ab initio MD simulations revealed that the introduction of O hinders the MG atoms from forming interfacial bonds with diamond, and reduces significantly the adhesion between the diamond tip and passivated MG. In addition, the synergistic effect of high hardness and elastic recovery associated with oxidization reduces ploughing friction and enhances wear resistance. This finding clarifies the importance of surface chemistry over structure modification during wear, and offers a generic pathway for tailoring ultra-wear resistant MGs.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

ObjectiveTo investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction (黄连解毒汤, HLJDD) in the treatment of Corona Virus Disease 2019 (COVID-19) through network pharmacology and molecular docking analysis. MethodsThe chemical constituents and action targets of HLJDD were retrieved on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SymMap v2, Encyclopedia of Traditional Chinese Medicine (ETCM), a High-throughput Experiment- and Reference-guided Database of Traditional Chinese Medicine (HERB), and Traditional Chinese Medicine Integrated Database (TCMID). UniProt and GeneCards were used to query the target genes that corresponding to the active compounds, and then a compound-target network was constructed using Cytoscape 3.7.2. Gene Ontology (GO) database was used to annotate GO functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to predict the possible mechanisms of active compounds. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analysis the tissue enrichment. The main active compounds in HLJDD are molecularly docked with their corresponding related targets. ResultsSeventy-six compounds were screened and 458 corresponding targets in the network were obtained. Gene annotation showed that the targets were involved mainly in 1953 biological processes. 884 signaling pathways was enriched, involving signaling by interleukins, cytokine signaling in immune system, generic transcription pathway, and RNA polymerase II transcription. The targets mainly distributed in the lung, liver, and placenta, involving a variety of immune cells, such as T cells and B cells. The molecular docking results showed that core compounds such as wogonin, berberine, and baicalein had high affinity with tumor necrosis factor (TNF), insulin (INS), and tumor protein 53 (TP53). ConclusionThe active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A (VEGFA), INS, interleukin-6 (IL-6), TNF, caspase-3 , TP53, and mitogen-activated protein kinase 3 (MAPK3).

Evading strength and ductility trade-off in an inverse nacre structured magnesium matrix nanocomposite

Mimicking nacre structure is an often-used strategy for developing materials which combine high strength and high toughness. Here, a novel strategy, named inverse nacre structure, is proposed where elongated and curled soft constituents are embedded in a matrix of hard constituent to form an ordered brick-and-mortar arrangement. This strategy is demonstrated in a particle reinforced metal matrix composite, using pure Mg as the soft phase and SiC nanoparticle reinforced Mg as the hard phase. The resulting nanocomposite yields high strength, and especially high tensile elongation which is five times that of the homogeneous counterpart. The superior comprehensive strengthening-toughening effect originates from the tailored inverse nacre structure which enables a stable microcrack-multiplication process by sufficiently promoting strain hardening so as to avoid any significant decrease in post-ultimate tensile strength. This strategy, while demonstrated here for the specific case of particle reinforced Mg, is not restricted to any particular material system but constitutes a generic pathway for the development of high-performance materials for engineering applications.

Pathway to encapsulate the surface water quality model and its applications as cloud computing services and integration with EDSS for managing urban water environments

The encapsulation of specific management measurements and computing services is rarely reported for surface water EDSS. To promote the efficiency and reduce the complexity of surface water EDSS development, a generic pathway to encapsulate the surface water quality model and its applications as cloud computing services is proposed. The web service is implemented under the OpenGMS framework. Two typical management measurements, water assimilative capacity allocation and pollution load reduction planning are encapsulated based on the advanced version of the WASP program. An EDSS instance of the Maozhou River, Shenzhen, is developed, which provides precise management measurements for COD and NH3–N control. Management services provided by other models, EFDC and SWMM, are also implemented under this novel framework. The proposed pathway provides the merits of rapid development, easy deployment, and maintenance of an advanced EDSS. It presents a good demonstration of coupling advanced WASP programs within EDSS for receiving water management.

Optimising access and provision of interventional radiology service to patients by utilising a new referral system.

Implementing a streamlined interventional radiology (IR) service in the UK has been a challenge. This study aims to review a set of changes introduced in IR at a tertiary centre, including a new referral process and the designation of IR clinical nurse specialists. A new process of referring patients to IR using a single generic referral pathway was implemented, replacing an order dropdown-based system. A qualitative survey was designed and distributed as a single-use web link in order to assess the satisfaction and impact of this new process. Responses were based on Likert scale and pertained to perceived qualities of the new referral process. Data analysis was performed to identify specialty and grade-specific trends and possible differences amongst groups. Findings from 98 respondents revealed a strong overall satisfaction with the new referral method and support for its continuation. Subgroup analysis by specialty, concluded medical specialties rated the new referral system more favourably than surgical specialties across all aspects: time efficiency, ease of use, periprocedural support and overall user experience. The new system also increased departmental productivity with an increase in the number of patients treated by 11.2%. Micropolicy changes within individual IR departments such as the replacement of a request-based referral system to one which puts IR in control of vetting and patient flow is one of many changes that reinforce the transformational phase of this specialty. Micropolicy changes within IR departments are key in the progression and widespread recognition of the specialty.

How Do Hospital Pharmacists Approach Substitution of Nanomedicines? Insights from a Qualitative Pilot Study and a Quantitative Market Research Analysis in Five European Countries.

We conducted research to assess hospital pharmacists’ familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid—follow-ons approved via the generic pathway), two biologic drugs (insulin glargine and etanercept—follow-ons approved via the biosimilar pathway), a non-biologic complex drug (NBCD; glatiramer acetate—follow-ons approved via the hybrid pathway) and a nanomedicine, ferric carboxymaltose (no follow-ons approved as yet). The study was conducted in two phases: an initial qualitative pilot study with 30 participants, followed by a quantitative stage involving 201 pharmacists from five European countries. Most expected negligible safety/efficacy differences between reference and follow-on products. Head-to-head clinical data showing therapeutic equivalence as a prerequisite for reference product/follow-on substitution was perceived to be needed most for biologics (47%), followed by NBCDs (44%)/nanomedicines (39%) and small molecules (23%). Overall, 28% did not know the data requirements for follow-on approval via the hybrid pathway; 16% were familiar with this pathway, compared with 50% and 55% for the generic and biosimilar pathways, respectively. Overall, 19% of respondents thought the European Medicines Agency (EMA) was responsible for defining the substitutability of follow-ons. Education is required to increase hospital pharmacist’s knowledge of regulatory approval frameworks and their relevance to substitution practices.

Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules

To enhance understanding of polycystic ovary syndrome (PCOS) at the molecular level; this investigation intends to examine the genes and pathways associated with PCOS by using an integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing data GSE84958 derived from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) between PCOS samples and normal controls were identified. We performed a functional enrichment analysis. A protein-protein interaction (PPI) network, miRNA- target genes and TF - target gene networks, were constructed and visualized, with which the hub gene nodes were identified. Validation of hub genes was performed by using receiver operating characteristic (ROC) and RT-PCR. Small drug molecules were predicted by using molecular docking. A total of 739 DEGs were identified, of which 360 genes were up regulated and 379 genes were down regulated. GO enrichment analysis revealed that up regulated genes were mainly involved in peptide metabolic process, organelle envelope and RNA binding and the down regulated genes were significantly enriched in plasma membrane bounded cell projection organization, neuron projection and DNA-binding transcription factor activity, RNA polymerase II-specific. REACTOME pathway enrichment analysis revealed that the up regulated genes were mainly enriched in translation and respiratory electron transport and the down regulated genes were mainly enriched in generic transcription pathway and transmembrane transport of small molecules. The top 10 hub genes (SAA1, ADCY6, POLR2K, RPS15, RPS15A, CTNND1, ESR1, NEDD4L, KNTC1 and NGFR) were identified from PPI network, miRNA - target gene network and TF - target gene network. The modules analysis showed that genes in modules were mainly associated with the transport of respiratory electrons and signaling NGF, respectively. We find a series of crucial genes along with the pathways that were most closely related with PCOS initiation and advancement. Our investigations provide a more detailed molecular mechanism for the progression of PCOS, detail information on the potential biomarkers and therapeutic targets.