A mixed-valent Fe(II)Fe(III) species converts cysteine to an oxazolone/thioamide pair in methanobactin biosynthesis.

SignificanceMethanobactins (Mbns), copper-binding peptidic compounds produced by some bacteria, are candidate therapeutics for human diseases of copper overload. The paired oxazolone-thioamide bidentate ligands of methanobactins are generated from cysteine residues in a precursor peptide, MbnA, by the MbnBC enzyme complex. MbnBC activity depends on the presence of iron and oxygen, but the catalytically active form has not been identified. Here, we provide evidence that a dinuclear Fe(II)Fe(III) center in MbnB, which is the only representative of a >13,000-member protein family to be characterized, is responsible for this reaction. These findings expand the known roles of diiron enzymes in biology and set the stage for mechanistic understanding, and ultimately engineering, of the MbnBC biosynthetic complex.

Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer.

BACKGROUND: Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. METHODS: BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. RESULTS: miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. CONCLUSION: This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.

Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Machine learning algorithms for prediction of entrapment efficiency in nanomaterials.

Exploitation of machine learning in predicting performance of nanomaterials is a rapidly growing dynamic area of research. For instance, incorporation of therapeutic cargoes into nanovesicles (i.e., entrapment efficiency) is one of the critical parameters that ensures proper entrapment of drugs in the developed nanosystems. Several factors affect the entrapment efficiency of drugs and thus multiple assessments are required to ensure drug retention, and to reduce cost and time. Supervised machine learning can allow for the construction of algorithms that can mine data available from earlier studies to predict performance of specific types of nanoparticles. Comparative studies that utilize multiple regression algorithms to predict entrapment efficiency in nanomaterials are scarce. Herein, we report on a detailed methodology for prediction of entrapment efficiency in nanomaterials (e.g., niosomes) using different regression algorithms (i.e., CatBoost, linear regression, support vector regression and artificial neural network) to select the model that demonstrates the best performance for estimation of entrapment efficiency. The study concluded that CatBoost algorithm demonstrated the best performance with maximum R2 score (0.98) and mean square error (< 10-4). Among the various parameters that possess a role in entrapment efficiency of drugs into niosomes, the results obtained from CatBoost model revealed that the drug:lipid ratio is the major contributing factor affecting entrapment efficiency, followed by the lipid:surfactant molar ratio. Hence, supervised machine learning may be applied for future selection of the components of niosomes that achieve high entrapment efficiency of drugs while minimizing experimental procedures and cost.

Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study).

BACKGROUND: This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. PATIENTS AND METHODS: Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. RESULTS: We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). CONCLUSION: Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.

miRNA expression in PCOS: unveiling a paradigm shift toward biomarker discovery.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects a substantial percentage of women, estimated at around 9-21%. This condition can lead to anovulatory infertility in women of childbearing age and is often accompanied by various metabolic disturbances, including hyperandrogenism, insulin resistance, obesity, type-2 diabetes, and elevated cholesterol levels. The development of PCOS is influenced by a combination of epigenetic alterations, genetic mutations, and changes in the expression of non-coding RNAs, particularly microRNAs (miRNAs). MicroRNAs, commonly referred to as non-coding RNAs, are approximately 22 nucleotides in length and primarily function in post-transcriptional gene regulation, facilitating mRNA degradation and repressing translation. Their dynamic expression in different cells and tissues contributes to the regulation of various biological and cellular pathways. As a result, they have become pivotal biomarkers for various diseases, including PCOS, demonstrating intricate associations with diverse health conditions. The aberrant expression of miRNAs has been detected in the serum of women with PCOS, with overexpression and dysregulation of these miRNAs playing a central role in the atypical expression of endocrine hormones linked to PCOS. This review takes a comprehensive approach to explore the upregulation and downregulation of various miRNAs present in ovarian follicular cells, granulosa cells, and theca cells of women diagnosed with PCOS. Furthermore, it discusses the potential for a theragnostic approach using miRNAs to better understand and manage PCOS.

COVID-19 vaccine and non-syndromic orofacial clefts in five arab countries. A case-control study.

OBJECTIVES: Risk factors for non-syndromic orofacial cleft (NSOFCs) include genetic profile and environmental exposure to medication and illnesses during pregnancy. We assessed the association between the COVID-19 vaccination and the incidence of NSOFC across five Middle Eastern countries. MATERIALS AND METHODS: This multi-country, hospital-based, case-control study included infants with NSOFCs whose first 3 intrauterine months coincided with the time when pregnant women were allowed to receive COVID-19 vaccination in the countries participating in the study. Newborns with NSOFCs were examined for cleft type and their parents were interviewed for maternal exposures and COVID-19 vaccination. Controls were newborns matched to cases in gender and setting. RESULTS: The study recruited 977 (348 children with NSOFCs and 629 controls). Maternal use of nicotine (Adjusted Odds Ratio (AOR): 2.437; P = 0.044) and family history of NSOFC (AOR: 11.059; P < 0.001) increased significantly the AOR of having a child with NSOFC. On the other hand, COVID-19 vaccine administration to pregnant mothers have significantly decreased the AOR of having a child with NSOFC (AOR: 0.337; P = 0.006). CONCLUSION: This study suggests that COVID-19 vaccination is not related to NSOFC and might protect against having a child affected with such a congenital anomaly. CLINICAL RELEVANCE: The finding of this study is important for healthcare providers for considering COVID-19 vaccination for pregnant woman. Clear communication and education about the potential risks and benefits would be crucial for informed decision-making. The study's results would directly impact pregnant individuals, as they would need accurate information to make informed decisions about their health and the health of their infants.

Influence of ß-catenin signaling on neurogenesis in neuropsychiatric disorders: Anxiety and depression.

It has been proven that stress, mainly in the early years of life, can lead to anxiety and mood problems. Current treatments for psychiatric disorders are not enough, and some of them show intolerable side effects, emphasizing the urgent need for new treatment targets. Hence, a better understanding of the different brain networks, which are involved in the response to anxiety and depression, may evoke treatments with more specific targets. One of these targets is ß-catenin that regulates brain circuits. ß-Catenin has a dual response toward stress, which may influence coping or vulnerability to stress response. Indeed, ß-catenin signaling involves several processes such as inflammation-directed brain repair, inflammation-induced brain damage, and neurogenesis. Interestingly, ß-catenin reduction is accompanied by low neurogenesis, which leads to anxiety and depression. However, in another state, this reduction activates a compensatory mechanism that enhances neurogenesis to protect against depression but may precipitate anxiety. Thus, understanding the molecular mechanism of ß-catenin could enhance our knowledge about anxiety and depression's pathophysiology, potentially improving clinical results by targeting it. Herein, the different states of ß-catenin were discussed, shedding light on possible drugs that showed action on psychiatric disorders through ß-catenin.

Hijacking 5-Fluorouracil Chemoresistance in Triple Negative Breast Cancer via microRNAs-Loaded Chitosan Nanoparticles.

Chemotherapy is still the mainstay of treatment for triple-negative breast cancer (TNBC) patients. Yet only 20% of TNBC patients show a pathologic complete response (pCR) after neoadjuvant chemotherapy. 5-Fluorouracil (5-FU) is a stable cornerstone in all recommended chemotherapeutic protocols for TNBC patients. However, TNBC patients' innate or acquired chemoresistance rate for 5-FU is steeply escalating. This study aims to unravel the mechanism behind the chemoresistance of 5-FU in the aggressive TNBC cell line, MDA-MB-231 cells, to explore further the role of the tumor suppressor microRNAs (miRNAs), miR-1275, miR-615-5p, and Let-7i, in relieving the 5-FU chemoresistance in TNBC, and to finally provide a translational therapeutic approach to co-deliver 5-FU and the respective miRNA oligonucleotides using chitosan-based nanoparticles (CsNPs). In this regard, cellular viability and proliferation were investigated using MTT and BrdU assays, respectively. 5-FU was found to induce JAK/STAT and PI3K/Akt/mTOR pathways in MDA-MB-231 cells with contaminant repression of their upstream regulators miR-1275, miR-615-5p, and Let-7i. Moreover, CsNPs prepared using the ionic gelation method were chosen and studied as nanovectors of 5-FU and a combination of miRNA oligonucleotides targeting TNBC. The average particle sizes, surface charges, and morphologies of the different CsNPs were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. In addition, the encapsulation efficiency (EE%), drug loading capacity (DLC%), and release manner at two different pH values were assessed. In conclusion, the novel CsNPs co-loaded with 5-FU and the combination of the three miRNA oligonucleotides demonstrated synergistic activity and remarkable repression in cellular viability and proliferation of TNBC cells through alleviating the chemoresistance to 5-FU.

Effect of prosthetic management of congenital cleft lip and palate on the middle ear function of infants: A clinical trial.

STATEMENT OF PROBLEM: Infants with a cleft palate often experience middle ear disease, a condition of great significance, and early prosthetic management of these infants is essential. However, any correlation between prosthetic palatal obturation and middle ear function is unclear. PURPOSE: The purpose of this clinical trial was to assess whether prosthetic palatal obturation with a feeding appliance prevented or improved middle ear problems in infants with a cleft lip and palate. MATERIAL AND METHODS: Ten infants with congenital cleft lip and palate (20 ears) were referred to the Prosthodontics department immediately after birth. Assessment of the middle ear function by tympanometry as well as hearing quality by auditory brainstem response (ABR) was conducted before the prosthetic treatment (control readings). The middle ear function and hearing quality was followed up after the prosthetic treatment every month until surgical palatal closure (tenth month). The Friedman test was applied to compare data from the various study periods. When the results were significant, the Dunn post hoc test was conducted to compare the control first week readings with those of the later periods (α=.05 for all tests). RESULTS: The preprosthetic readings of tympanometry in the first week were 90% Type A and 10% Type B for both right and left ears. Readings starting from the first to the fifth month revealed no statistically significant differences compared with the first week readings (P>.05). However, tympanometry readings starting from the sixth month (20% Type A and 80% Type B) until the tenth month (90% Type B and 10% Type C) for both ears represented a statistically significant difference compared with the first week readings (P≤.05). The preprosthetic readings of ABR in the first week showed that 90% of ears had normal hearing status and 10% had mild hearing loss. Readings starting from the first until the fifth month revealed no statistically significant differences compared with the first week readings (P>.05). However, ABR readings starting from the sixth month (20% normal hearing, 70% mild hearing loss, and 10% moderate hearing loss) until the tenth month (0% normal hearing, 80% mild hearing loss, and 20% moderate hearing loss) for both ears revealed a statistically significant difference compared with the first week readings (P≤.05). CONCLUSIONS: Prosthetic palatal obturation with a feeding appliance plays a role in delaying rather than preventing the occurrence of otitis media with effusion in infants with a cleft lip and palate and could reduce the need for ventilation tubes.

Oral health status of Egyptian children with lysosomal storage diseases: An evaluation of dental indices, salivary cytokines level, and bacterial bioburden.

BACKGROUND: Lysosomal storage diseases (LSDs), a group of inborn errors of metabolism, include various subtypes, for example, mucopolysaccharidosis (MPS) and Gaucher disease (GD). Besides the physical/mental disabilities, they suffer from several oral deteriorations. AIM: To evaluate the oral health status of Egyptian children with LSD. DESIGN: Thirty LSD children and thirty non-LSD children were enrolled for this study according to the inclusion and exclusion criteria. Dental indices were used to assess caries prevalence and periodontal status. Saliva samples were collected from all enrolled children to estimate interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and protein levels as well as Streptococcus mutans and Lactobacilli colony counts. RESULTS: Children with MPS and GD showed non-significant differences in decayed, missing, or filled teeth (DMFT) scores (p = .115). Scores of dmft showed a significant increase in MPS, but not in GD children (p = .020, p = .127). Children with LSD showed significantly increased Modified Gingival Index (MGI), Plaque Index (PI), Oral Hygiene Index (OHI-s) scores (p < .001) and salivary IL-6 and TNF-α (p = .007, p = .001, p < .0001, p = .002, respectively) and salivary total proteins (p = .001) levels. Unexpectedly, non-significant differences were observed in salivary Streptococcus mutans or Lactobacilli counts in children with MPS and GD (p = .058, p = .420, p = .502, p = .053, respectively). CONCLUSION: To our knowledge, this is the first article that evaluates Egyptian children with LSD. We demonstrated high caries prevalence in primary teeth, not permanent teeth, in children with MPS and poor gingival/hygiene status in children with MPS and GD, which triggered a state of inflammation. The daily supplement intake prevented oral bacterial growth. The most probable cause of oral alterations is decreased salivary flow rate, as deduced from a significantly increased salivary protein.

Flexural strength, flexural modulus and microhardness of milled vs. fused deposition modeling printed Zirconia; effect of conventional vs. speed sintering.

BACKGROUND: Various methods can be used for creating zirconia dental restorations, including 3-dimensional (3D) printing and computer-aided design/ computer-aided manufacturing (CAD/CAM) milling. The fused deposition modeling (FDM) printing method for zirconia presents numerous advantages, albeit research on the mechanical properties of these materials and resultant restorations remains scarce. Such developments are undeniably intriguing and warrant further investigation. The objective of the present study was to evaluate the impact of the sintering firing cycle (Conventional vs. Speed sintering) on the flexural strength, flexural modulus, and Vickers Microhardness of milled vs. FDM printed zirconia. METHODS: A total of 60 bars (2 × 5 × 27 mm) were fabricated for flexural strength testing, along with 40 discs (12 × 1.5 mm) for Vickers microhardness testing. Half of the specimens underwent conventional sintering, while the other half underwent a speed sintering cycle. The flexural strength and modulus were determined by a three-point bending test in a universal testing machine. The microhardness of the specimens was evaluated using a Vickers microhardness tester. Statistical analysis was performed using a two-way ANOVA test with a post-hoc Tukey test (p < 0.05). RESULTS: CAD/CAM milled zirconia had significantly higher flexural strength and modulus than FDM-printed zirconia. The sintering process did not significantly affect the flexural strength or modulus of milled or FDM-printed zirconia. The milled speed sintering group had significantly higher values in the Vickers microhardness test compared to the other groups. CONCLUSIONS: The mechanical properties of FDM-printed zirconia specimens were not found to be comparable to those of milled zirconia. Speed sintering cycle may produce milled zirconia restorations with similar flexural strength and modulus to conventional sintering, and even higher Vickers Microhardness values.

Effect of prosthetic management and its timing on otological and audiological outcomes in infants with cleft lip and palate: A clinical trial.

PURPOSE: To evaluate how prosthetic management affects the otological and audiological state of infants with cleft lip and palate by preventing or treating otitis media (OM). MATERIALS AND METHODS: Thirty infants with cleft lip and palate (L/P) were assigned to three equal groups according to the age of prosthetic intervention; Group I: immediately after birth, Group II: 2 months old, Group III: 5 months old. Assessment of middle ear function by tympanometry and hearing quality by auditory brainstem response (ABR) under natural sleep was conducted before and after prosthetic treatment every month till 10 months of age. Data from the study groups were compared. RESULTS: No statistically significant differences were found between Gp I and Gp II in the 2nd, 3rd, and 4th months for right and left ears (p > 0.05). In the 5th month, statistically significant differences between the three groups were found in tympanometry for right (p = 0.011) and left (p = 0.024) ears also, in ABR for right (p = 0.007) and left (p = 0.011) ears. Tympanometric readings starting from the 6th till the 10th month showed no statistically significant differences between the three groups (p >0.05). The final ABR outcomes of the 10th month indicated statistically significant differences between the three groups for both ears (p = 0.027). CONCLUSIONS: Early prosthetic care could delay the development of OM, so it could potentially improve the otological and audiological state in infants with cleft L/P. However, prosthetic treatment may not be able to completely prevent or eliminate middle ear disorders.

Oral health related knowledge, attitude and behavior among group of mothers in relation to their primary school children's oral health: a cross-sectional study.

The etiology of oral diseases in children is complex and multifactorial. The oral health of children can be influenced by various factors, including parental knowledge, attitudes and behaviors, as well as socioeconomic status. The objective of this study was to assess, among mothers of children aged 6-12 years, (1) mothers' knowledge about their children's oral health, (2) mothers' attitude toward their children's oral health, and (3) mothers' dental behavior concerning their oral health and to evaluate their influence on their children's dental caries. This cross-sectional study involved three questionnaires to be filled in by mothers of primary school children in addition to an oral examination of their children to measure decayed, missing, filled teeth for primary (dmft) and permanenet (DMFT) dentitions. The mother-child pairs were recruited through multistage stratified random sampling of primary schools in Jeddah, Saudi Arabia. The questionnaire was comprised of four sections: 1-demographic characteristics and socioeconomic status 2-Hiroshima University Dental Behavioral Inventory (mothers' attitudes and behavior pertaining to their oral health) 3-mothers' knowledge regarding the oral health of their children 4-mothers' attitude toward their children oral health. A total of 1496 mother-child pairs completed the study. The mean values of dmft were 4.08 ± 3.47; DMFT was 1.82 ± 2.07; total dmft and DMFT were 5.65 ± 4.05. According to the questionnaire results, mothers in private schools had a more favorable attitude and behavior toward their oral health, as well as a more favorable knowledge and attitude toward their children's oral health. The multiple linear regression model revealed that children's dmft/DMFT scores were significantly related to mother education, mother questionnaire scores, and the Simplified Oral Hygiene Index. Children's oral health is significantly impacted by oral health-related knowledge, attitude and behaviors of their mothers in addition to income status and education level.

Decoding hepatocarcinogenesis from a noncoding RNAs perspective.

Being a leading lethal malignancy worldwide, the pathophysiology of hepatocellular carcinoma (HCC) has gained a lot of interest. Yet, underlying mechanistic basis of the liver tumorigenesis is poorly understood. The role of some coding genes and their respective translated proteins, then later on, some noncoding RNAs (ncRNAs) such as microRNAs have been extensively studied in context of HCC pathophysiology; however, the implication of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in HCC is indeed less investigated. As a subclass of the ncRNAs which has been elusive for long time ago, lncRNAs was found to be involved in plentiful cellular functions such as DNA, RNA, and proteins regulation. Hence, it is undisputed that lncRNAs dysregulation profoundly contributes to HCC via diverse etiologies. Accordingly, lncRNAs represent a hot research topic that requires prime focus in HCC. In this review, the authors discuss breakthrough discoveries involving lncRNAs and circRNAs dysregulation that have contributed to the contemporary concepts of HCC pathophysiology and how these concepts could be leveraged as potential novel diagnostic and prognostic HCC biomarkers. Further, this review article sheds light on future trends, thereby discussing the pathological roles of lncRNAs and circRNAs in HCC proliferation, migration, and epithelial-to-mesenchymal transition. Along this line of reasoning, future recommendations of how these targets could be exploited to achieve effective HCC-related drug development is highlighted.

Community based peer-led TB screening intervention: an innovative approach to increase TB knowledge, presumptive case identification, and referral among sexual minority people in urban Bangladesh.

INTRODUCTION: One of the contributors to tuberculosis (TB) burden among vulnerable populations, such as sexual minority people, is the delay in case finding and notification. Given their socially excluded, hard-to-reach nature, community-led approaches need to be introduced to facilitate their screening of TB symptoms and their subsequent referral to TB healthcare providers. This article aimed to explore the existing challenges surrounding TB screening and referral, and the implementation facilitators and barriers of the proposed community-based TB screening model for sexual minority people in Dhaka, Bangladesh. METHODS: This study followed the quasi-experimental design using mixed methods (i.e., qualitative and quantitative) approach. The study participants who were also a part of the community-led TB screening model included sexual minority people enrolled in HIV prevention interventions. In addition to quantitative inquiry, in-depth interviews were conducted on sexual minority people, focus group discussions were also conducted on them and HIV prevention service providers, and key-informant interviews were conducted on service providers, programmatic experts and TB researchers. Data were analyzed using content, contextual and thematic approaches. RESULTS: The 'Six Steps in Quality Intervention Development' framework was used to guide the development of the community-based TB screening model. In Step 1 (identifying the problem), findings revealed low rates of TB screening among sexual minority people enrolled in the HIV prevention intervention. In Step 2 (identifying contextual factors for change), various individual, and programmatic factors were identified, which included low knowledge, low-risk perception, prioritization of HIV services over TB, and stigma and discrimination towards these populations. In Step 3 (deciding change mechanism), community-based screening approaches were applied, thus leading to Step 4 (delivery of change mechanism) which designed a community-based approach leveraging the peer educators of the HIV intervention. Step 5 (testing intervention) identified some barriers and ways forward for refining the intervention, such as home-based screening and use of social media. Step 6 (collecting evidence of effectiveness) revealed that the main strength was its ability to engage peer educators. CONCLUSION: This study indicates that a community-based peer-led TB screening approach could enhance TB screening, presumptive TB case finding and referral among these populations. Therefore, this study recommends that this approach should be incorporated to complement the existing TB program.

Are we ready for a sustainable approach? A qualitative study of the readiness of the public health system to provide STI services to the key populations at risk of HIV in Bangladesh.

INTRODUCTION: In Bangladesh, sexually transmitted infection (STI) services are available for all populations in public health facilities. However, STI services for key populations (KPs) at risk of HIV need specifically designed approaches that are predominantly administered to KPs through donor-supported service centers operated by non-government organizations (NGOs) and community-based organisations (CBOs). However, the steady decline in donor funding warrants a sustainable transition of STI services for the KPs into public health facilities. This article aimed to explore the service availability and readiness of public health facilities to provide STI services for the KPs. METHODS: This qualitative study explored the service availability and readiness of public health facilities in three districts of Bangladesh by adapting the Service Availability and Readiness Assessment tool. We conducted 34 in-depth interviews,11 focus group discussions with KPs, and 29 key-informant interviews with healthcare providers, researchers, programme implementers and policy planners, in addition to series of direct observations at the public healthcare facilities. Data were analysed through thematic analysis, and categorised in relation to the WHO building blocks. RESULTS: This study revealed that the public health system was generally not ready to serve the KPs' needs in terms of providing them with quality STI services. The 'service delivery' component, which is the most crucial facet of the public health system, was not ready to provide STI services to KPs. Findings also indicated that health workforce availability was limited in the primary and secondary healthcare layers but adequate in the tertiary layer, but needed to be oriented on providing culturally sensitised treatment. Counseling, an essential component of STI services, was neither ready nor available. However, health information systems and a few other components were partially ready, although this warrants systematic approaches to address these challenges. CONCLUSION: The findings show that public health facilities are yet to be fully ready to render STI services to KPs, especially in terms of service delivery and human and health resources. Therefore, it is not only integral to mobilize communities towards the uptake of public health services, but health systems need to be prepared to cater to their needs.

Heat Shock Proteins: Central Players in Oncological and Immuno-Oncological Tracks.

Heat shock proteins (HSPs) are a group of proteins that promote protein folding, inhibit denaturation of cellular proteins, and maintain other proteins' functional activities when cells are subjected to stress and/or high temperature. HSP classification is generally based on their molecular weights into large and small HSP. The family of small HSPs includes HSPs 27, 40, 60, 70, and 90. The potential roles of HSP27 and HSP70 are quite evident in different solid malignancies, including breast, colorectal, pancreatic, and liver cancers. In this chapter, the authors focus on HSP27 and HSP70 signaling in oncology and their role in different solid malignancies as well as they shed light on the novel role of HSP70 and HSP90 in the immune-oncology field.

Prenatal maternal stress and the severity of autism spectrum disorder: A cross-sectional study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to several genetic and environmental factors including antenatal stress. Hence, we aimed to examine whether a mother's stress during pregnancy is associated with the severity of autism spectrum disorder in children. The study was conducted with 459 mothers of children with autism (aged 2-14 years) who were attending rehabilitation and educational centers in the two major cities of Makkah and Jeddah in Saudi Arabia. Environmental factors, consanguinity, and ASD family history were assessed using a validated questionnaire. The Prenatal Life Events Scale questionnaire was used to assess whether the mothers were exposed to stress during pregnancy. Two models of ordinal regression analysis were conducted including gender, child age maternal age, parental age, maternal education, parental education, income nicotine exposure, mother taking medication during pregnancy, family history of ASD, gestation, consanguinity, exposure of prenatal life events (in model 1), and severity of prenatal life events (in model 2). Family history of ASD showed a statistically significant association with the severity of ASD in both regression models (p = .015, odds ratio [OR]: 4.261 in Model 1, and p = .014, OR: 4.901 in model 2). In model 2, the moderate severity prenatal life events showed higher statistically significant adjusted odds ratio for ASD severity compared to no stress (p = .031; OR: 3.82). Within the limitations of this study, prenatal stressors showed some potential contribution to ASD severity. Family history of ASD was the only factor that showed a persistent association with ASD severity. A study that assesses the effect of COVID-19 stress on ASD prevalence and severity is recommended.