Splenic complications in pediatric sickle cell disease: A retrospective cohort review.

OBJECTIVE: To delineate the natural history of splenic complications other than loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children's Hospital. METHODS: We determined the dates of diagnoses of splenic complications, the number of acute splenic sequestration crises (ASSC), and hydroxyurea treatment in pediatric patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC. RESULTS: The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of splenic complications was highest in patients with hemoglobin Sß0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sß+. The overall event rate of ASSC was 8.3 per 100 patient-years. The event-rate was 28.4 for hemoglobin Sß0, 10.9 for hemoglobin SS, and 3.5 for hemoglobin SC. Patients with hemoglobin SS and hemoglobin Sß0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event rates of 14.2 and 3.1, respectively. The event rate was also higher for children who started hydroxyurea before age 2 years than for those who started after this age (19.8 and 9.2, respectively). CONCLUSIONS: The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sß0 having the most severe complications. Hydroxyurea therapy is associated with increased incidence of ASSC, particularly when initiated before 2 years of age.

Small extracellular vesicles: Multi-functional aspects in non-small cell lung carcinoma.

Extracellular vesicles (EVs) impact normal and pathological cellular signaling through bidirectional trafficking. Exosomes, a subset of EVs possess biomolecules including proteins, lipids, DNA fragments and various RNA species reflecting a speculum of their parent cells. The involvement of exosomes in bidirectional communication and their biological constituents substantiate its role in regulating both physiology and pathology, including multiple cancers. Non-small cell lung cancer (NSCLC) is the most common lung cancers (85%) with high incidence, mortality and reduced overall survival. Lack of efficient early diagnostic and therapeutic tools hurdles the management of NSCLC. Interestingly, the exosomes from body fluids similarity with parent cells or tissue offers a potential future multicomponent tool for the early diagnosis of NSCLC. The structural twinning of exosomes with a cell/tissue and the competitive tumor derived exosomes in tumor microenvironment (TME) promotes the unpinning horizons of exosomes as a drug delivery, vaccine, and therapeutic agent. Exosomes in clinical point of view assist to trace: acquired resistance caused by various therapeutic agents, early diagnosis, progression, and surveillance. In an integrated approach, EV biomarkers offer potential cutting-edge techniques for the detection and diagnosis of cancer, though the purification, characterization, and biomarker identification processes for the translational research regarding EVs need further optimization.

Mesenchymal stem cell-derived exosomes: Characteristics and applications in disease pathology and management.

Mesenchymal stem cells (MSCs) possess a role in tissue regeneration and homeostasis because of inherent immunomodulatory capacity and the production of factors that encourage healing. There is substantial evidence that MSCs' therapeutic efficacy is primarily determined by their paracrine function including in cancers. Extracellular vesicles (EVs) are basic paracrine effectors of MSCs that reside in numerous bodily fluids and cell homogenates and play an important role in bidirectional communication. MSC-derived EVs (MSC-EVs) offer a wide range of potential therapeutic uses that exceed cell treatment, while maintaining protocell function and having less immunogenicity. We describe characteristics and isolation methods of MSC-EVs, and focus on their therapeutic potential describing its roles in tissue repair, anti-fibrosis, and cancer with an emphasis on the molecular mechanism and immune modulation and clinical trials. We also explain current understanding and challenges in the clinical applications of MSC-EVs as a cell free therapy.

GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.

Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.

Anticipating undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry: a decision tool for bronchial challenge testing.

BACKGROUND: Some patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing. OBJECTIVE: To determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT). METHODS: Using random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC20) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated. RESULTS: Of 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered 'yes' to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72-0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT. CONCLUSIONS: Four readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required.

MSX1 Gene Polymorphisms in Patients with non-Syndromic Cleft lip and Palate: A Tertiary Care Centre Based Case-Control Study from Central Kerala.

OBJECTIVE: The purpose of this study was to investigate the contribution of MSX1 gene polymorphisms to the risk of developing NSCLP. DESIGN: Case-Control Study. SETTING: A tertiary care centre. PATIENTS/PARTICIPANTS: The sample consisted of 200 subjects (100 cases and 100 controls). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Genotyping was performed by restriction fragment length polymorphism. Allele and genotype frequencies were calculated between patients and controls and analyzed using online Web Tools such as SISA and SNPstats. The MSX1 gene polymorphisms c. 799 GT, c.458 CA can be risk factors in the development of orofacial clefts. RESULTS: In the cases, an association was found between NSCLP and c.799 and c.458 of the MSX1 gene when compared with the control. The dominant and overdominant models, c. 799 GT, c.458 CA genotypes and c. 799 T, c.458 A alleles in the population are said to be the main risk factors to develop the NSCLP in our study population. The genotype variation of c 799 G/T and c.458 C/A are revealed to be specifically contributing to an NSCLP-type Cleft lip and Palate. It is worth noting that NSCLP females in the study population showed a stronger association with heterozygous genotypes of c.799 and c.458. However, further investigation with a larger cohort is necessary to confirm these findings. CONCLUSION: Overall the results of the study revealed that MSX1 c 799 G > T and c.458 C > A can be considered as one of the genetic risk factors in the formation of Non-Syndromic Cleft Lip and Palate in the study population.

Real-World Effectiveness of COVID-19 Vaccine and Identification of SARS-CoV-2 Variants among People Living with HIV on Highly Active Antiretroviral Therapy in Central Kerala of India-An Ambi-Directional Cohort Study.

BACKGROUND: Vaccine effectiveness for first-generation coronavirus disease (COVID-19) vaccines among People Living with HIV (PLHIV) in India remains unexplored. This study entails the estimation of the real-world effectiveness of COVID-19 vaccines (AZD1222/Covishield, BBV152/Covaxin) among PLHIV and the identification of variants of SARS-CoV-2 among those infected with COVID-19. METHODS: An ambi-directional cohort study was conducted among 925 PLHIV above 18 years of age in two districts of central Kerala, India, from February 2022 to March 2023. Selected PLHIV were recruited as Participant Liaison Officers (PLOs) for the follow-up on the study participants. At enrolment, basic details, baseline CD4 count, and a Nasopharyngeal (NP) swab for RT-PCR were collected. In the follow-up phase, NP swabs were collected from subjects with COVID-19 symptoms. Positive subjects had a CD4 count and genomic sequencing performed. RESULTS: The mean age of the participants was 46.93 ± 11.00 years. The majority, 819 (93.6%), of participants had received at least one dose of any vaccine, while 56 (6.4%) were unvaccinated. A total of 649 (79.24%) participants were vaccinated with Covishield and 169 (20.63%) with Covaxin. In the vaccinated group, 158 (19.3%) reported COVID-19 infection. Vaccine Effectiveness (VE) for one dose of any vaccine was 43.2% (95% CI: 11.8-64.5), p = 0.015. The effectiveness of full vaccination with Covishied was 63.8% (95% CI: 39.3-79.2), p < 0.001, and Covaxin was 73.4% (95% CI: 44.3-87.3). VE was highest, at 60.7% (95% CI: 23.6-81.3), when the two doses of the vaccine were given at an interval of less than 6 weeks. Participants with a baseline CD4 count > 350 had greater protection from COVID-19, at 53.4% (95% CI: 19.6-75.3) p = 0.004. The incident cases were sub-variants of Omicron (BA.2, BA.2.38, BA.2.10). CONCLUSIONS: Full vaccination with Covishield and Covaxin was effective against COVID-19 infection among PLHIV on treatment; albeit, that of Covaxin was higher. A gap of 4 to 6 weeks between the two doses of COVID-19 vaccine was found to have higher VE among PLHIV.

miRNAs in the prognosis of triple-negative breast cancer: A review.

Triple-Negative Breast Cancer (TNBC) is a highly aggressive and invasive type of breast cancer (BC) with high mortality rate wherein effective target medicaments are lacking. It is a very heterogeneous group with several subtypes that account for 10-20% of cancer among women globally, being negative for three most important receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)), with an early and high recurrence resulting in poor survival rate. Therefore, a more thorough knowledge on carcinogenesis of TNBC is required for the development of personalized treatment options. miRNAs can either promote or suppress tumorigenesis and have been linked to a number of features of cancer progression, including proliferation, metastasis, apoptosis, and epithelial-mesenchymal transition (EMT). Recent miRNA research shows that there is great potential for the development of novel biomarkers as they have emerged as drivers of tumorigenesis and provide opportunities to target various components involved in TNBC, thus helping to solve this difficult-to-treat disease. In this review, we summarize the most relevant miRNAs that play an essential role in TNBC biology. Their role with regard to molecular mechanisms underlying TNBC progression has been discussed, and their potential use as therapeutic or prognostic markers to unravel the intricacy of TNBC based on the pieces of evidence obtained from various works of literature has been briefly addressed.

Novel biomolecules in targeted cancer therapy: a new approach towards precision medicine.

Cancer is a major threat to human life around the globe, and the discovery of novel biomolecules continue to be an urgent therapeutic need that is still unmet. Precision medicine relies on targeted therapeutic strategies. Researchers are better equipped to develop therapies that target proteins as they understand more about the genetic alterations and molecules that cause progression of cancer. There has been a recent diversification of the sorts of targets exploited in treatment. Therapeutic antibody and biotechnology advancements enabled curative treatments to reach previously inaccessible sites. New treatment strategies have been initiated for several undruggable targets. The application of tailored therapy has been proven to have efficient results in controlling cancer progression. Novel biomolecules like SMDCs, ADCs, mABs, and PROTACS has gained vast attention in the recent years. Several studies have shown that using these novel technology helps in reducing the drug dosage as well as to overcome drug resistance in different cancer types. Therefore, it is crucial to fully untangle the mechanism and collect evidence to understand the significance of these novel drug targets and strategies. This review article will be discussing the importance and role of these novel biomolecules in targeted cancer therapies.

Protective effects of macromolecular polyphenols, metals (zinc, selenium, and copper) - Polyphenol complexes, and different organs with an emphasis on arsenic poisoning: A review.

For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment's effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.

Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics.

Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (NSCLC), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in NSCLC therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and NSCLC management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage NSCLC, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance.

Onco-Pathogen Mediated Cancer Progression and Associated Signaling Pathways in Cancer Development.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8-17% of the world's cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers.

Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy.

Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells' potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment.

Dynamics of the accommodative response and facility with dual-focus soft contact lenses for myopia control.

OBJECTIVE: To assess the impact of using dual-focus soft contact lenses for myopia control on the dynamics of the accommodative response and facility. METHODS: 24 young adult myopes were fitted with dual-focus soft contact lenses for myopia control (MiSight®) and single-vision soft contact lenses (Proclear®). The WAM-5500 open-field autorefractor was used to measure the dynamics of the accommodative response (magnitude and variability) in binocular conditions, with accommodative data being gathered from the dominant eye, at three viewing distances (500 cm, 40 cm, and 20 cm) during 90 s. Also, the binocular accommodative facility was assessed with the WAM-5500 autorefractor. All participants performed the same experimental protocol with the dual-focus (MiSight) and single-vision (Proclear) soft contact lenses, with both experimental sessions being carried in two different days and following a counterbalanced order. RESULTS: This study showed greater lags of accommodation with the MiSight than the Proclear lenses at near distances (40 cm: 1.27 ± 0.77 vs. 0.68 ± 0.37 D, corrected p-value = 0.002, Cohen-d = 0.90; and 20 cm: 1.47 ± 0.84 vs. 1.01 ± 0.52 D, corrected p-value = 0.007, Cohen-d = 0.75), whereas a higher variability of accommodation was observed with the dual-focus than the single-vision lenses at 500 cm (0.53 ± 0.11 vs. 0.23 ± 0.10 D), 40 cm (0.82 ± 0.31 vs. 0.68 ± 0.37 D), and 20 cm (1.50 ± 0.56 vs. 1.15 ± 0.39 D) (corrected p-value < 0.001 in all cases, and Cohen-ds = 0.67-2.33). Also, a worse quantitative (27.75 ± 8.79 vs. 34.29 ± 10.08 cycles per minute, p = 0.029, Cohen-d = 0.48) and qualitative (23.68 ± 7.12 vs. 28.43 ± 7.97 score, p = 0.039, Cohen-d = 0.45) performance was observed with the MiSight when compared to the Proclear lenses. CONCLUSIONS: The use of dual-focus soft contact lenses for myopia control alters the dynamics of accommodative response and facility in the short-term. Although this optical design has demonstrated its effectiveness for myopia control, eye care specialists should be aware of the acute effects of these lenses on accommodation performance.

Effect of wearing different types of face masks during dynamic and isometric resistance training on intraocular pressure.

CLINICAL RELEVANCE: The use of face masks has demonstrated to be an effective strategy to prevent transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Wearing face masks, mainly Filtering Face Piece 2 (FFP2) masks, during exercise practice has demonstrated to affect several physiological measures. BACKGROUND: This study was aimed at assessing the intraocular pressure (IOP) behaviour during the execution of the dynamic and isometric biceps-curl exercise with a surgical and FFP2 face mask. METHODS: Twenty two physically active young adults performed sets of 10 repetitions against the 10-RM (repetition maximum) load and 1-minute isometric effort against a load 15% lower than the 10-RM load with the FFP2 and surgical mask and without any mask. A total of six exercise sets (3 experimental conditions [FFP2, surgical and control] × 2 exercise modalities) were performed. A rebound tonometer was used to measure IOP before, during (10 measurements), and after (30-seconds of passive recovery) each training set. RESULTS: At rest, there were not statistically significant IOP differences (p = 0.222). During dynamic exercise, there was a progressive IOP rise (p < 0.001), and a higher IOP response with the FFP2 than without the mask (corrected p-value = 0.003). For the isometric exercise, there was a greater IOP response as a function of accumulated effort (p < 0.001), which was dependent of the face mask used (FFP2> surgical>control; corrected p-values< 0.01). CONCLUSIONS: The FFP2 masks cause a heightened IOP response during the execution of dynamic and isometric biceps-curl exercise, suggesting that, when possible, glaucoma patients should limit the use of FFP2 masks during resistance training.

Data clustering: application and trends.

Clustering has primarily been used as an analytical technique to group unlabeled data for extracting meaningful information. The fact that no clustering algorithm can solve all clustering problems has resulted in the development of several clustering algorithms with diverse applications. We review data clustering, intending to underscore recent applications in selected industrial sectors and other notable concepts. In this paper, we begin by highlighting clustering components and discussing classification terminologies. Furthermore, specific, and general applications of clustering are discussed. Notable concepts on clustering algorithms, emerging variants, measures of similarities/dissimilarities, issues surrounding clustering optimization, validation and data types are outlined. Suggestions are made to emphasize the continued interest in clustering techniques both by scholars and Industry practitioners. Key findings in this review show the size of data as a classification criterion and as data sizes for clustering become larger and varied, the determination of the optimal number of clusters will require new feature extracting methods, validation indices and clustering techniques. In addition, clustering techniques have found growing use in key industry sectors linked to the sustainable development goals such as manufacturing, transportation and logistics, energy, and healthcare, where the use of clustering is more integrated with other analytical techniques than a stand-alone clustering technique.

Implications of cancer stem cells in diabetes and pancreatic cancer.

This review provides a detailed study of pancreatic cancer (PC) and the implication of different types of cancers concerning diabetes. The combination of anti-diabetic drugs with other anti-cancer drugs and phytochemicals can help prevent and treat this disease. PC cancer stem cells (CSCs) and how they migrate and develop into malignant tumors are discussed. A detailed explanation of the different mechanisms of diabetes development, which can enhance the pancreatic CSCs' proliferation by increasing the IGF factor levels, epigenetic modifications, DNA damage, and the influence of lifestyle factors like obesity, and inflammation, has been discussed. It also explains how cancer due to diabetes is associated with high mortality rates. One of the well-known diabetic drugs, metformin, can be combined with other anti-cancer drugs and prevent the development of PC and has been taken as one of the prime focus in this review. Overall, this paper provides insight into the relationship between diabetes and PC and the methods that can be employed to diagnose this disease at an earlier stage successfully.

The mechanism of action of non-coding RNAs in placental disorders.

Placental complication arises due to various risk factors occurring during the pregnancy period, leading to an increased morbidity rate. Placenta related disorders are one of primary reason for pregnancy related complications and the clinical incidences are seen to be on the rise. Most of the common disorders associated with placenta are pre-eclampsia, recurrent spontaneous abortions, intra-uterine growth restriction etc. Several studies have been done to understand the genetics and immunological attributes leading to the development of placenta associated complications. In the recent years, studies were able to establish and identify ncRNAs found specifically in foetal tissues such as the placenta. The aberrant expression patterns of ncRNA associated with placenta has been linked to disorders such as pre-eclampsia. Since ncRNA play a major role in regulating biological processes like trophoblast growth, migration and invasion, their aberrant expression could very well lead to complications like spontaneous pregnancy loss. This review article focuses on the association of ncRNAs - miRNAs, lncRNAs, CircRNAs in placenta associated complications as well as the different ncRNA based therapies. Deciphering the exact mechanism involved in the regulation and development of placenta through ncRNA will help in using it as a biomarker for early diagnosis. Understanding the therapeutic opportunities of ncRNAs in placental disorders will result in better treatment strategies.

Advances in the Lung Cancer Immunotherapy Approaches.

Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains. Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised. Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions. We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements.