BACKGROUND Spinal cord ischemia-reperfusion injury (IRI), which can occur as a result of temporary aortic occlusion during resection of thoracoabdominal aneurysms, can be an unpredictable and devastating complication of aortic surgery. There are no specific medications or guidelines for the prevention and treatment of spinal cord IRI (SCIRI). It is now known that IRI not only exacerbates local tissue damage when blood flow is restored but also affects distant organs, such as the liver, lungs, and brain, through mediators released into the systemic circulation. Studies show that ozone pretreatment reduces oxidative damage by increasing antioxidant capacity, promotes anti-inflammatory signaling, improves blood circulation, and ameliorates IRI. Our study is one of the first to examine the effects of ozone on remote organs (liver, lung, and brain) when administered via different routes (intrathecal, intraperitoneal, rectal) in a spinal cord ischemia-reperfusion model. AIM To determine whether ozone administered by different routes offers multiorgan protection in SCIRI. METHODS Thirty adult Wistar albino rats were randomly divided into five groups (n = 6, each): A control (C group), an IR group, an IR rectal ozone (IRRO) group, an IR intrathecal ozone (IRITO), and an IR intraperitoneal ozone (IRIPO). In the IR groups, the spinal cord IR models (a 30-minute ischemia period was applied to the infrarenal abdominal aorta using an atraumatic vascular clamp, and then a 120-minute reperfusion period was applied by removing the clamp) were applied. An ozone-oxygen mixture of 1 mg/kg (50 μg/mL) was administered by rectal insufflation to the IRRO group, 0.7 mg/kg (50 μg/mL) via the peritoneum to the IRIPO group, and 20 μL (20 μg/mL) intrathecally to the IRITO group 30 minutes before midline laparotomy. At the end of the reperfusion procedure, histopathological and biochemical analyses of liver, lung, and brain tissues were performed. RESULTS Liver tissue malondialdehyde (MDA) levels were significantly lower, and catalase (CAT) enzyme activities were significantly higher in the IRRO, IRITO, and IRIPO groups than in the IR group. Histopathologically, we had favorable results from all three ozone applications compared to the IR group. Lung tissue MDA levels were significantly lower, and CAT enzyme activities were significantly higher in the IRITO and IRIPO groups than in the IR group. We had more positive results in the IRRO group than in the IR group, but the difference was not found to be significant. Histopathologically, we obtained significantly more positive results in the IRITO and IRIPO groups compared with the IR group regarding all the criteria we evaluated. Our results in the IRRO group were also positive. Brain tissue MDA levels were significantly lower and CAT enzyme activities significantly higher in the IRITO and IRIPO groups than in the IR group. We had positive results in the IRRO group compared with the IR group. Histopathologically, we obtained significantly more positive results in the IRITO group regarding all the criteria we evaluated. CONCLUSION We observed histopathologically that single-dose ozone pretreatment administered intrathecally, intraperitoneally, or rectally had positive effects on liver, lung, and brain tissues compared to the IR group in an SCIRI model in rats due to its antioxidant effect. The best histopathological results were obtained with intrathecal, intraperitoneal, and rectally administered ozone, in that order, in all three tissues.
Pulmonary embolism (PE) is a common and potentially fatal thromboembolic disease contributing to a major global public health burden. Its pathogenesis involves multiple hemodynamic, inflammatory, metabolic, and genetic factors. The multifactorial nature of PE makes it difficult to infer the direct effects of risk factors using conventional statistical approaches because of potential confounding and reverse causality. Mendelian randomization (MR) uses genetic variants as instrumental variables to strengthen causal inference. This narrative review synthesizes the available MR literature concerning potential causative factors of PE, with particular emphasis on genetic and biological pathways. MR evidence suggests that matrix metalloproteinases (MMP)-19 may be associated with increased PE susceptibility, whereas MMP-12 may be associated with decreased susceptibility. Impaired kidney function showed a positive association with PE risk, and reduced HLA-DR+ NK cell traits were linked to PE pathogenesis. Among gut microbiota, Clostridium innocuum was associated with increased PE risk, whereas Butyricicoccus and Actinobacteria showed protective associations. No consistent causal associations were identified for type 2 diabetes, atrial fibrillation, or epigenetic age acceleration. Larger multiethnic studies integrating multi-omics data are needed to clarify mechanisms underlying PE pathogenesis.
BACKGROUND Diagnosing growth hormone deficiency (GHD) in children remains challenging because of the considerable variability in the results of growth hormone (GH) provocative tests. AIM To evaluate the validity of different GH provocative tests, determine the sampling time associated with the peak GH response, and identify optimal GH cut-off values for excluding GHD. METHODS This cohort study included 50 children aged 5-16 years presenting with proportionate short stature. GH secretion was stimulated using the insulin tolerance test, clonidine test, and levodopa (L-DOPA) test. Serum GH and insulin-like growth factor-1 levels were measured using commercially available enzyme-linked immunosorbent assay kits. RESULTS Among the studied participants, 48% were diagnosed with GHD, while 52% were classified as having idiopathic short stature. The clonidine stimulation test showed the highest median GH level at 90 minutes, followed by the insulin-induced peak at 45 minutes and the L-DOPA peak at 60 minutes. A statistically significant positive correlation was observed between the insulin-like growth factor-1 Z-score and the GH level measured at 90 minutes during the clonidine test. Receiver operating characteristic curve analysis demonstrated optimal GH cut-off values of 7.54 ng/mL for the insulin test, 8.48 ng/mL for the clonidine test, and 4.63 ng/mL for the L-DOPA test. These cut-offs showed sensitivities of 59.3%, 77.8%, and 80%, and specificities of 91.3%, 82.6%, and 70%, respectively. CONCLUSION Oral clonidine and L-DOPA stimulation tests appear to be useful and safe alternatives for diagnosing GHD, avoiding the risk of hypoglycemia associated with the insulin tolerance test. Lower GH peak cut-off values may improve the diagnostic performance of these provocative tests.
We read with great interest the recent articles by Chandrabalan et al on diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) and by Kodiyatar et al on adjuvant herbal therapies. These articles provide important insights into DKA in T2DM, both at a clinical and experimental level. However, further endocrine aspects need to be addressed. In one study a paradoxical relationship between pre-admission metformin use and reduced in-hospital mortality from DKA was noted; this may be related to preserved beta-cell function and a more favorable incretin-glucagon axis rather than a pharmacological effect per se . However, important endocrine effectors such as C-peptide, glucagon, and incretin hormones were not measured. Furthermore, currently available antidiabetic agents, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have not been taken into account despite their possible effects on ketogenesis. An additional and underappreciated complexity is the concurrent occurrence of acute pancreatitis (AP) in DKA patients (DKA-AP), a complication that may affect at least 15% of DKA cases and that can neutralize key clinical and biochemical features of each condition, confounding diagnosis and worsening prognosis. At the same time, studies on Gymnema sylvestre have shown promising effects on glycemia and metabolism, while their endocrine effects have not been fully characterized. Recent data have shown possible effects of this herbal preparation on glucocorticoid receptors, suggesting a possible impact on the hypothalamus-pituitary-adrenal axis. We propose that future studies take into account detailed hormonal profiles and systematic screening for concurrent AP, which could help to further clarify the pathophysiology and mechanisms of currently available agents in T2DM-associated DKA.
BACKGROUND Lupus nephritis (LN) is a significant cause of kidney morbidity in patients with systemic lupus erythematosus. While glomerular lesions are the primary focus of current classifications, tubulointerstitial involvement may significantly influence renal outcomes. There is limited data on tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) in Middle Eastern populations. AIM To examine the clinical, pathological, and prognostic significance of coexisting TII and TID in patients with biopsy-proven LN from Saudi Arabia. METHODS We retrospectively analyzed 100 patients with biopsy-confirmed LN. Patients were stratified into those with TII + TID (n = 48) and those without (n = 52). Baseline demographics, clinical features, laboratory and immunological data, and histopathological findings, including modified National Institutes of Health (NIH) activity and chronicity scores, were collected. Multivariable logistic regression identified predictors of TII + TID. Renal response during follow-up was evaluated using Kaplan-Meier analysis, and predictors of adverse composite outcomes were assessed using Cox regression. RESULTS Patients with TII + TID had lower baseline estimated glomerular filtration rate (77.7 ± 37.4 mL/minute/1.73 m2 vs 98.2 ± 52.7 mL/minute/1.73 m2; P = 0.028) and higher low-density lipoprotein cholesterol (LDL-C; 3.01 ± 1.88 mmol/L vs 1.78 ± 1.82 mmol/L; P = 0.006). They also had higher modified NIH activity (6.17 ± 3.90 vs 3.13 ± 3.18; P < 0.001) and chronicity scores (4.21 ± 1.74 vs 1.85 ± 2.44; P < 0.001). Proliferative classes, especially class III (35.4% vs 15.4%) and class IV + V (20.8% vs 15.4%; P = 0.024), were more common in this group. Independent predictors of TII + TID included class III (OR = 150.42; P = 0.006), class IV + V (OR = 44.11; P = 0.03), LDL-C (OR = 2.26; P = 0.004), fibrinoid necrosis [Exp(B) = 2.29; P = 0.041], and interstitial inflammation [Exp(B) = 73.29; P < 0.001]. Patients with TII + TID had slower and reduced rates of achieving renal remission. Higher baseline serum creatinine, older age, elevated C-reactive protein (CRP), and the presence of hyaline deposits were associated with worse composite renal outcomes. In contrast, total glomerulosclerosis showed an inverse association in the subgroup but not in the overall cohort. CONCLUSION TII and damage are common in LN and are closely associated with proliferative glomerular lesions, fibrinoid necrosis, and adverse renal outcomes. The presence of TII + TID, along with baseline creatinine, CRP, and hyaline deposits, identifies patients at higher risk for poor renal prognosis. These findings highlight the importance of evaluating the tubulointerstitial compartment for risk stratification and tailored management in LN, particularly in the Saudi Arabian population.
The problem of heart failure (HF) is complicated and is continuously growing, making the need for novel solutions critical. The role of melatonin, widely used as an over-the-counter medication for sleep disorders, has been historically researched for its cardioprotective actions based on its established antioxidant properties. Recent preliminary evidence, however, points to a possibly alarming association: A statistically significant increased risk of new onset HF, HF requiring hospitalization, and all-cause mortality was observed in association with long-term melatonin therapy (one year or longer in duration), in adult patients suffering from insomnia. However, these were reported in a single, as-yet unpublished conference abstract that has not undergone peer review or independent validation. This hypothesis-generating observation warrants careful investigation of possible mechanisms. In this article we speculatively propose a plausible - but as yet unconfirmed - mechanistic pathway mediated through prolactin (PRL). Melatonin may increase the release of PRL through its modulation of hypothalamic dopaminergic neurons, though whether this effect is sustained with long-term use remains an unresolved critical knowledge gap. This is particularly relevant given that peripartum cardiomyopathy, a dangerous, pregnancy-related variant of HF, has as its central mechanism the cardiotoxic effect of a cytotoxic 16-kDa fragment of PRL. We hypothesize that chronic exogenous melatonin use might - if it were shown to sustain hyperprolactinemia - provide excess PRL that could theoretically be cleaved to the cardiotoxic 16-kDa fragment in patients with pre-existing oxidative stress and cardiovascular risk factors, in a manner analogous to peripartum cardiomyopathy. This speculative mechanism should be tested in prospective mechanistic and clinical studies, with appropriate adjustment for confounders including insomnia severity.
BACKGROUND Urinary tract infections (UTIs) are prevalent worldwide, and Escherichia coli (E. coli ) is the most common causative agent. The ability of the bacteria to form intracellular bacterial communities (IBCs) and biofilm is a major reason for UTIs. Studies have indicated that the persistence of uropathogenic E. coli as IBCs and biofilms has been implicated in UTIs. However, IBCs are not routinely identified by standard diagnostic methods. AIM To compare the various staining techniques for the detection of IBCs in urine samples from E. coli culture-positive UTI patients with the biofilm-forming capability of the isolates. METHODS The study included 73 patients with E. coli culture-confirmed UTI. Before antibiotic treatment midstream urine sample was collected, and the sediment was obtained by centrifugation. The samples were visualized using Sternheimer-Malbin, Wright-Giemsa, Safranin, and immunofluorescence staining to detect IBCs. Formation of biofilms was analyzed by the tube method. Descriptive statistics were used. RESULTS E. coli clusters were seen by light microscopy using various stains. However, immunofluorescence staining showed a better picture in the form of bright intracellular signals, which indicate bacterial aggregates. Biofilm assay showed an association with intracellular colonization. CONCLUSION The various staining techniques help in the identification of uropathogenic E. coli as IBCs inside superficial epithelial cells. These bacteria are also capable of forming biofilms, which resists action of antibiotics. Thus, IBCs and biofilms are rich reservoirs of organisms in the urinary bladder, paving the way for chronic treatment-resistant UTIs. This study requires further larger studies to substantiate these findings.
We read with interest the article by Rusman et al published in World Journal of Experimental Medicine. Beyond microbial composition, the gut-liver axis is a rhythmic system regulated by a bidirectional interaction between host clocks and the gut microbiota. Social jetlag induces "temporal dysbiosis", disrupting the timing of metabolites and compromising the intestinal barrier, which exacerbates metabolic injury in metabolic dysfunction-associated steatotic liver disease. Restoration of these rhythms through chronotherapeutic approaches provides an effective method to restore alignment and improve clinical outcomes. Specifically, social jetlag desynchronizes hepatic clocks and disrupts microbially-modified bile acid signaling, promoting fat accumulation. Chronotherapeutic strategies like time-restricted eating can effectively mitigate disease progression by "reprogramming" the liver transcriptome and reducing hepatic triglycerides.
The six-minute walk test (6MWT) remains a tool for assessing exercise capacity in heart failure, with six-minute walk distance as the endpoint. To enhance interpretability, vital signs such as heart rate and blood pressure may also be recorded in accordance with technical statements. However, beta-blockers often blunt heart-rate-based readouts during the 6MWT, thereby reducing the interpretability of six-minute walk distance. Akimova et al recently published a study in World Journal of Experimental Medicine , which identified blood pressure variability (BPV) as a minutes-scale recovery signal during a paired 6MWT. The index targets the 20-minute post-exercise recovery window and uses point-to-point systolic blood pressure change to help characterize cardiac reserve and to enhance interpretation of the 6MWT. The measure is low cost and easy to implement, and BPV remains associated with imaging indices such as left ventricular ejection fraction in beta-blocked heart failure populations. Importantly, this should be viewed as an early, proof-of-concept insight. Future work should confirm these findings in multicenter prospective studies, define operational protocols and thresholds for BPV, and explore relationships with clinical outcomes, thereby further enhancing the value of minutes-scale BPV.
Ocular involvement in pediatric acute leukemia is an increasingly recognized, clinically relevant manifestation, but prevalence and patterns vary. It may arise from direct leukemic infiltration or secondary hematologic abnormalities. Recent observational studies, including Eastern India cohorts, underscore systematic ophthalmic evaluation at diagnosis. In a cohort of 47 children by Parija et al published in the World Journal of Experimental Medicine , ocular findings were present in 40.4% at presentation; most were asymptomatic and retinal hemorrhages predominated. Other series report similar patterns, with retinal hemorrhages common and prevalence roughly 40%-45%, while pooled meta-analytic estimates suggest an overall prevalence near 20%, differences likely reflect ethnicity, healthcare access, diagnostic protocols, study design, and sample size. Hematologic factors such as anemia and thrombocytopenia favor hemorrhagic lesions, whereas marked leukocytosis and high blast counts associate with infiltrative involvement of the retina, optic nerve, or orbit. Although some studies link ocular involvement to higher disease burden and worse outcomes, evidence is inconsistent because of methodological limitations and short follow-up. These findings support routine baseline ophthalmic screening, even in asymptomatic children, to detect vision-threatening lesions and clearly inform risk assessment. Larger prospective studies with standardized ocular and hematologic correlations are needed to define prognostic significance and optimize screening.
We read with great interest the study by Yadav et al published in the World Journal of Experimental Medicine , which postulated a nomogram including patient’s critical factors, other than urine sample. European Association of Urology (EAU) published the guidelines on urological infection 2025. The EAU guidelines 2025 of urinary infections (UIs) has classified in two distanced categories: Localized UTs and systemic UTs according to specific patient’s symptoms and clinical signs, this new practical classification replaced previous concept of non-complicated urinary tract infection (UTI) against complicated UTI. The new EAU classification categorizes UIs as either localized or systemic, according to the presence of specific clinical signs and symptoms, this new practical classification replaced previous concept of non-complicated UTI against complicated UTI, irrespective of the results of bacteriological findings. In the new classification of UIs, the classification is based on clinical set-up on which the practitioner or urologist will manage the patient. Management of UIs is crucial to consider the urinary and gut microbiota. It was established recently that antibiotic use affects microbiota homeostasis in the gut and urinary tract that will initiate dysbiosis.
BACKGROUND Dysregulated signal transducer and activator of transcription 3 (STAT3) signaling is a key feature of human papillomavirus (HPV)-driven cervical carcinogenesis. Our earlier work demonstrated elevated STAT3 expression plays a regulatory role in oncogenic transcription of HPV16 E6/E7. A combined analysis of STAT3 and HPV E6/E7 mRNA by fluorescence in situ hybridization (FISH) showed diagnostic clinical relevance in screening for pre-cancerous cervical lesions. However, use of FISH does not provide clear objective diagnostic threshold to establish accurate signal positivity. AIM To assess the feasibility of FISH for quantitative detection of STAT3 and HPV E6/E7 transcripts using a flow cytometry-based approach. METHODS HPV-negative (C33a), HPV16-positive (SiHa) and HPV18-positive (HeLa) cervical cancer cell lines were analyzed for STAT3 and HPV E6/E7 transcript expression using FISH approach. Signal specificity and distribution were assessed by fluorescence microscopy using target-specific and scrambled probes. The same probes were further evaluated using flow cytometry-based FISH to determine their suitability for quantitative transcript detection. RESULTS Fluorescence microscopy revealed strong and discrete STAT3-associated signals in SiHa and HeLa cells, whereas C33a cells exhibited comparatively diffuse fluorescence. Scrambled control probes produced minimal background staining, supporting the specificity of STAT3 probe. HPV16 E6 probe also produced detectable signals but comparable fluorescence intensity was observed across all cell lines irrespective of HPV status and was similar to scrambled probe controls. Moreover, when assessed by flow cytometry-based FISH, the same probes displayed limited performance. STAT3-positive populations were low and accounted for approximately 10% of cells, while no clearly distinguishable HPV16 E6-positive population could be identified in any of the tested cell lines. These findings indicate that optimized microscopy-based FISH assay may not be directly compatible with flow-based transcript detection platforms. CONCLUSION Therefore, re-optimization of assay is required for quantitative transcript detection for HPV-associated cervical cancer screening using flow cytometry-based FISH. The manuscript addresses the bottlenecks and potential strategies to mitigate the issues.
BACKGROUND Staphylococcus aureus (S. aureus ) is one of the six highly pathogenic nosocomial bacteria. These bacteria develop or evolve with several antibiotic resistance mechanisms and therefore known to escape antibiotic treatments. Several reports suggest that multidrug resistance in S. aureus is increasing worldwide over the time. Indian population is comprised of diverse ethnic group residing different geographical regions. Recent reports revealed that antibiotic resistance in S. aureus isolates vary in different regions of India. AIM To identify antibiotic resistance pattern in S. aureus in India. METHODS In the present study, we overviewed resistance in S. aureus isolates to different antibiotics. We searched for the research articles on antibiotic resistance in S. aureus from India using Scopus, Google scholar, and PubMed databases (Prospero registration No. PROSPERO 2025CRD420251153034). We identified a total of 26 articles published during 2013 to 2024 in English language. We extracted the information about the location of the study, antibiotics used and percentage of the resistant isolates. RESULTS Among 26 studies, most of the studies were reported from northern India (31%), southern India (27%) and eastern India (27%), followed by western India (11%) and Pan India (4%). The findings highlight very high resistance to beta-lactam antibiotics, particularly penicillin and methicillin, reflecting a substantial burden of methicillin-resistant S. aureus . Fluoroquinolones and macrolides also showed elevated resistance levels, whereas linezolid, teicoplanin, chloramphenicol, and doxycycline retained comparatively better activity. CONCLUSION The present review, demonstrated geographical region wise trends of antibiotic resistance in S. aureus from India, which will be useful in designing the further studies investigating antibiotic resistance patterns.
A critical work published by Panchannavar et al on the close link between oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), the expression of epithelial mesenchymal transition proteins ZEB1 and E-cadherin would predict the progression of OLK to OSCC. In connection with similar clinical status, there are cumulative data that the urinary bladder leukoplakia (Bladder-LK) progress to invasive bladder squamous cell carcinoma (SCC) which does not response to local therapy that indicates immediate cystectomy, these findings were established with multiple publications with clinical follow-up that showed the progression of leukoplakia to SCC in both oral cavity and urinary bladder. Oral leukoplakia, oral SCC, Bladder-LK, urothelial carcinoma (UC) of the bladder, squamous differentiation of UC, and bladder-SCC showed expression of programmed cell death-ligand 1 (PD-L1). In recent years, immune checkpoint inhibitors immunotherapy for malignant tumors became a promising cancer immunotherapy. However, the role of PD-L1 inhibitors in OLK OSCC is controversial. Objectives are to highlight the rationale for prospective treatment of OLK and OSCC with PD-L1 inhibitors immunotherapy.
Very low-density lipoprotein (VLDL), released in the liver, is the only lipoprotein that includes apolipoprotein B (marker for cardiovascular risk), triglycerides, and cholesterol. VLDL is essential in transporting lipids and cholesterol to organs and cells for utilization. VLDL also contributes significantly to the advancement of atherosclerotic heart disease. We comprehensively summarize VLDL’s physiological roles and data supporting its pathological effects. VLDL has been proven to promote atherosclerosis in the metabolic syndrome. VLDL isolated from metabolic syndrome patients is cytotoxic to atrial myocytes, causing atrial myopathy and contributing to atrial fibrillation. Several endocrine diseases may impact VLDL levels, which can be boosted by supplementing with progesterone, estrogen, cortisol, and growth hormones. VLDL stimulates high blood pressure by secreting aldosterone. VLDL induces neuroinflammation, which may lead to cognitive impairment. VLDL is linked to chronic renal illness, autoimmune disorders, and some skin diseases. VLDL production outside the liver caused by intestinal dysbiosis is considered harmful. New evidence reveals that VLDL metabolism has a role in the development and risk of cancer, as well as sleep disturbances. Aside from this, VLDL metabolism and carcinogenesis might be altered by the VLDL receptor. Overall, growing findings point to the role of VLDL in many illnesses.
BACKGROUND Periodontitis is a chronic inflammatory disease triggered by a polymicrobial challenge to the periodontium. While scaling and root planing (SRP) is the gold standard for treatment, its efficacy is often limited by incomplete pathogen eradication and rising antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT) has emerged as a potent adjunctive treatment, utilizing light-activated photosensitizers to induce targeted bacterial lysis. Specifically, the delivery of indocyanine green (ICG) via chitosan nanoparticles (CNPs) may enhance stability and penetration, offering a synergistic approach to improving clinical outcomes when combined with SRP. AIM To evaluate the overall improvements in various clinical and microbiological periodontal parameters in periodontitis patients undergoing aPDT with CNPs-ICG. METHODS Thirty periodontitis patients having interdental clinical attachment loss (CAL) ‘detectable’ at ≥ 2 non-adjacent teeth, buccal or oral CAL ≥ 3 mm with pocketing > 3 mm detectable at ≥ 2 teeth were randomly assigned to aPDT with CNPs-ICG + SRP (test) group and conventional SRP + laser irradiation only (control) group in a split-mouth design. At baseline, 1-month and 3-months plaque index (PI), modified sulcular bleeding index, pocket probing depth (PPD) and relative clinical attachment level (RCAL) and microbiological tests were recorded. RESULTS The test group showed more improvement in PPD (7 mm to 3.26 mm in 1-month and 3.13 mm in 3-months) and RCAL (12 mm to 8.26 mm in 1 month and 8.4 mm in 3 months) than control group that showed PPD reduction from 6.7 mm (at baseline) to 3.73 mm at 1-month and 3.76 mm at 3 months and RCAL reduction from 12.23 mm (at baseline) to 8.7 mm at 1-month and 8.9 mm at 3-months with a statistically significant difference (P = 0.001). The test sites showed a statistically significant (P = 0.001) increase in negative microbiological test results (from 10% at baseline to 80% at 1 month and 3 months follow-up) compared to control sites (6.7% at both baseline and 1-month and 3-months follow-up). CONCLUSION aPDT using CNPs-ICG + SRP can be considered as a better procedure in improving periodontal clinical parameters like PPD and RCAL and in reducing periodontal pathogens than conventional SRP alone.
N6-methyladenosine (m6A) is the most prevalent internal RNA modification in eukaryotic transcripts, and YTH structural domain family (YTHDF) 2 is a principal m6A reader that governs RNA stability and turnover. Accumulating evidence indicates that YTHDF2 exerts context-dependent and sometimes opposing functions across major neurological disorders, including Alzheimer’s disease, Parkinson’s disease, glioblastoma, epilepsy, and experimentally induced cognitive and neuropsychiatric conditions. By selectively promoting decay of m6A-marked transcripts - such as leucine rich repeat and immunoglobulin domain containing 2, axis inhibition protein 1, breast cancer type 1 susceptibility protein associated protein 1, mitogen-activated protein kinase kinase 4, family with sequence similarity 134 member B, and NOD-like receptor family pyrin domain-containing 3 - YTHDF2 modulates diverse processes including amyloid processing, Wnt signaling, ferroptosis, neuroinflammation, metabolic homeostasis, and autophagy. Its activity is further shaped by upstream regulatory pathways (e.g. , epidermal growth factor receptor-SRC proto-oncogene, non-receptor tyrosine kinase-extracellular signal-regulated kinase and protein arginine methyltransferase 6-cyclin-dependent kinase 9) and by dynamic interplay with m6A writers and erasers, including methyltransferase like 14 and fat mass and obesity-associated protein. This mini-review synthesizes recent mechanistic advances, emphasizes regional and cell-type heterogeneity of YTHDF2 function, and proposes a “dose-target dependency” framework to reconcile its bidirectional effects. We also outline emerging translational strategies aimed at evaluating YTHDF2 as a mechanistic biomarker and a selectively tractable therapeutic target in neurological disease.
