Decoding dysregulated genes, molecular pathways and microRNAs involved in cervical cancer.

BACKGROUND: The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV. METHODS: We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection. RESULTS: In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1. CONCLUSIONS: The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.

Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths.

Malaria, a life-threatening infectious disease caused by Plasmodium falciparum, remains a significant global health challenge, particularly in tropical and subtropical regions. The epidemiological data for 2021 revealed a staggering toll, with 247 million reported cases and 619,000 fatalities attributed to the disease. This formidable global health challenge continues to perplex researchers seeking a comprehensive understanding of its pathogenesis. Recent investigations have unveiled the pivotal role of extracellular vesicles (EVs) in this intricate landscape. These tiny, membrane-bound vesicles, secreted by diverse cells, emerge as pivotal communicators in malaria's pathogenic orchestra. This Review delves into the multifaceted roles of EVs in malaria pathogenesis, elucidating their impact on disease progression and immune modulation. Insights into EV involvement offer potential therapeutic and diagnostic strategies. Integrating this information identifies targets to mitigate malaria's global impact. Moreover, this Review explores the potential of EVs as diagnostic biomarkers and therapeutic targets in malaria. By deciphering the intricate dialogue facilitated by these vesicles, new avenues for intervention and novel strategies for disease management may emerge.

Microneedle based transcutaneous delivery of low molecular weight heparin.

This study aimed to fabricate and characterize polymeric microneedle patches for rapid and non-invasive administration of enoxaparin across skin layers. The patches comprising of PVA, sorbitol and enoxaparin sodium were prepared by employing micromolding technique. Formulated patches were characterized physicochemically by folding endurance, dimensional analysis and swelling study, morphologically by optical and scanning electron microscopy and thermally by thermogravimetric analysis. Moreover, performance efficiency of prepared polymeric device was analyzed by in-vitro drug release study and piercing ability. Prepared patches showed appropriate dimensions and folding endurance (i.e., ~1100) indicating satisfactory integrity of polymeric device. Patches exhibited appropriately distanced needles with pointed tips in optical and scanning electron microscopy analysis. Thermogravimetric analysis proved thermal stability of formulation ingredients and prepared patches. Swelling percentage was >110 % suggesting that prepared formulation would allow penetration of physiological fluids in its polymeric network. Maximum (~89%) drug was released within ~2 hours during in-vitro release study. In-vitro piercing ability experiments suggested that prepared patches successfully breached skin barrier stratum corneum. It is concluded that prepared microneedle device can serve as a potential alternative of currently employed invasive parenteral route for rapid and efficient administration of enoxaparin sodium in the systemic circulation.

Enhanced Neurokinin-1 Receptor Expression Is Associated with Human Dental Pulp Inflammation and Pain Severity.

Substance P (SP) is a peptide involved in many biological processes, including nociception and inflammation. SP has a high affinity for its receptor neurokinin-1 (NK-1R). SP/NK-1R complex plays a major role in the interactions going on during the onset of dental pain and inflammation. Objective. To identify the expression of NK-1R in healthy and inflamed human dental pulp, as well as to identify any association with severity of dental pain. Methods. This case-control study included ten irreversibly inflamed samples of dental pulp, which were extirpated from patients presenting with chief complaint of dental pain due to caries. Ten healthy pulps, extirpated from those teeth which were indicated for extraction due to orthodontic reasons, were used as the control group. Visual analog scale (VAS) and modified McGill Pain Questionnaire were used to assess the characteristic and severity of pain. Immunohistochemical study was performed using monoclonal antibodies against NK-1R. Results. The results showed that the NK-1R was expressed intensely in patients with higher pain score. The mean pain score in cases was 7.0 ± 2.0. The healthy dental pulps had negative or mild NK-1R staining of +1 intensity. The NK-1R score in cases was 2.4 ± 0.516 and 0.2 ± 0.4216 in controls. There was significant difference in NK-1R score between both groups (p value <0.05). There was a strong positive correlation between the pain score and NK-1R expression score. As the pain increased, the NK-1R expression score was also increased (0.95∗∗, p value 0.000). Conclusions. NK-1R is overexpressed in inflamed dental pulp. SP/NK-1R modulation may provide a novel approach for the treatment of pulpal inflammation and pain.

Improved transdermal delivery of cetirizine hydrochloride using polymeric microneedles.

PURPOSE: The aim of this study was to design and characterize microneedle patch formulation containing cetirizine hydrochloride. METHODS: Chitosan was co-formulated with cetirizine hydrochloride. Transdermal patches were prepared by casting this solution to microneedle molds. Control patches were formulated by casting this solution to a plain cuvet of same area as mold but lacking microneedles. An array of methods namely; differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) were employed for the characterization of the films and the microneedles accordingly whereas in vitro permeation studies were conducted across rat skin. Light microscopy was performed to assess any histological changes upon microneedles application onto the rat skin. RESULTS: The patches had a reproducible thickness (0.86 ± 0.06 mm) and folding endurance. Both the blank and drug loaded patches had 100 microneedles each of 300 micrometre length. In addition, the microneedle patches were ascribed with a two-fold increase in drug permeation across rat skin in the presence of microneedles as compared to the control formulations. Histological examination confirms a minimal invasion of the skin conferred by the microneedles. CONCLUSION: The microneedle patches serve as an alternate route of drug administration in patients with nausea and swelling difficulties. Graphical abstract Microneedle patch manifest a two-fold increase in the skin permeation of Cetirizine Hydrochloride as compared to the control that is drug loaded patch without microneedles.

Treatment of cardiac nocardiosis in a post-renal transplant patient of systemic nocardiosis.

In general, nocardia infects immunosuppressed patients, however, sometimes it can also infect immunocompetent individuals. Nocardia infection can disseminate to any organ system of the body but the pulmonary system is the most commonly involved system. In some rare cases, the heart can also be involved and the resulting cardiac mycetoma can be treated successfully with antimicrobials without the need of surgery, unlike fungal cardiac mycetomas wherein surgery may be required in addition to antimicrobial therapy. We present an interesting case of post-renal transplant cardiac nocardiosis, which was treated successfully with a course of antibiotics.

Maternal near miss and quality of maternal health care in Baghdad, Iraq.

BACKGROUND: The maternal near-miss concept has been developed as an instrument for assisting health systems to evaluate and improve their quality of care. Our study aimed at studying the characteristics and quality of care provided to women with severe complications in Baghdad through the use of the World Health Organization (WHO) near-miss approach for maternal health. METHODS: This is a facility-based, cross-sectional study conducted in 6 public hospitals in Baghdad between March 1, 2010 and the June 30, 2010. WHO near-miss approach was utilized to analyze the data in terms of indicators of maternal near miss and access to and quality of maternal care. RESULTS: The maternal near-miss rate was low at 5.06 per 1,000 live births, while the overall maternal near miss: mortality ratio was 9:1. One third of the near-miss cases were referred from other facilities and the mortality index was the same for referred women and for in-hospital women (11%). The intensive care unit (ICU) admission rate was 37% for women with severe maternal outcomes (SMO), while the overall admission rate was 0.28%. Anemia (55%) and previous cesarean section (45%) were the most common associated conditions with severe maternal morbidity. The use of magnesium sulfate for treatment of eclampsia, oxytocin for prevention and treatment of postpartum hemorrhage, prophylactic antibiotics during caesarean section, and corticosteroids for inducing fetal lung maturation in preterm birth is suboptimum. CONCLUSIONS: The WHO near-miss approach allowed systematic identification of the roadblocks to improve quality of care and then monitoring the progress. Critical evidence-based practices, relevant to the management of women experiencing life-threatening conditions, are underused. In addition, possible limitations in the referral system result in a very high proportion of women presenting at the hospital already in a severe health condition (i.e. with organ dysfunction). A shortage of ICU beds leading to women taken care of without admission to ICU may also contribute to a high proportion of maternal deaths and organ dysfunction.