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1.
Pathol Res Pract ; 258: 155303, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38728793

ABSTRACT

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

2.
Ageing Res Rev ; : 102327, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38734148

ABSTRACT

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

3.
World J Gastrointest Surg ; 16(4): 1097-1108, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38690043

ABSTRACT

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity. It aids in significant weight loss and improves obesity-related medical conditions. Despite its effectiveness, postoperative care still has challenges. Clinical evidence shows that venous thromboembolism (VTE) is a leading cause of 30-d morbidity and mortality after RYGB. Therefore, a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates. AIM: To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB. METHODS: Using the 2016-2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program, data from 6526 patients (body mass index ≥ 40 kg/m2) who underwent RYGB were analyzed. A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB. The resultant risk scores were derived from the coefficients of statistically significant variables. The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation. RESULTS: Of the 26 initial variables, six predictors were identified. These included a history of chronic obstructive pulmonary disease with a regression coefficient (Coef) of 2.54 (P < 0.001), length of stay (Coef 0.08, P < 0.001), prior deep venous thrombosis (Coef 1.61, P < 0.001), hemoglobin A1c > 7% (Coef 1.19, P < 0.001), venous stasis history (Coef 1.43, P < 0.001), and preoperative anticoagulation use (Coef 1.24, P < 0.001). These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB. The risk model's area under the curve (AUC) was 0.79 [95% confidence interval (CI): 0.63-0.81], showing good discriminatory power, achieving a sensitivity of 0.60 and a specificity of 0.91. Without training, the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63 (95%CI: 0.62-0.64) and endoscopic sleeve gastroplasty with an AUC of 0.76 (95%CI: 0.75-0.78). CONCLUSION: This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients, offering insights into factors that heighten the risk of VTE events.

4.
Pathol Res Pract ; 258: 155329, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38692083

ABSTRACT

Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.

5.
Sci Total Environ ; 931: 172967, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38705297

ABSTRACT

The fascinating world of microscopic life unveils a captivating spectacle as bacteria effortlessly maneuver through their surroundings with astonishing accuracy, guided by the intricate mechanism of chemotaxis. This review explores the complex mechanisms behind this behavior, analyzing the flagellum as the driving force and unraveling the intricate signaling pathways that govern its movement. We delve into the hidden costs and benefits of this intricate skill, analyzing its potential to propagate antibiotic resistance gene while shedding light on its vital role in plant colonization and beneficial symbiosis. We explore the realm of human intervention, considering strategies to manipulate bacterial chemotaxis for various applications, including nutrient cycling, algal bloom and biofilm formation. This review explores the wide range of applications for bacterial capabilities, from targeted drug delivery in medicine to bioremediation and disease control in the environment. Ultimately, through unraveling the intricacies of bacterial movement, we can enhance our comprehension of the intricate web of life on our planet. This knowledge opens up avenues for progress in fields such as medicine, agriculture, and environmental conservation.


Subject(s)
Bacteria , Bacterial Physiological Phenomena , Chemotaxis , Biodegradation, Environmental
6.
J Oncol Pharm Pract ; : 10781552241245332, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38576329

ABSTRACT

INTRODUCTION: Acute pancreatitis (AP) following drug-induced hypertriglyceridemia is a rare clinical phenomenon. Immune checkpoint inhibitors have revolutionized treatment for a variety of solid organ and hematological malignancies. Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has shown promising responses in many advanced cancers. However, a constellation of immune-related adverse events has also been described. There are reports of pembrolizumab-induced hypertriglyceridemia, but AP as a result of this side effect remains an exceedingly rare clinical sequela. CASE REPORT: We delineate a case of a patient with stage IVB non-small-cell lung cancer who developed progressive abdominal pain and nausea following administration of pembrolizumab for four months. Laboratory studies revealed increased serum lipase and triglyceride levels at 12,562 IU/L and 16,901 mg/dL, respectively. The diagnosis of AP was made based on the revised Atlanta classification criteria. After ruling out alternative causes, pembrolizumab-induced hypertriglyceridemia was considered the likely etiology of AP. MANAGEMENT AND OUTCOME: The patient was transferred to the medical intensive care unit for close monitoring. Treatment was initiated with intravenous fluids, pain medications, and an insulin infusion. However, her hypertriglyceridemia levels remained persistently elevated, necessitating therapeutic apheresis. She recovered well with no complications after triglyceride apheresis. DISCUSSION: AP following pembrolizumab-associated hypertriglyceridemia remains a rare clinicopathologic entity. Given the widespread clinical use of immune checkpoint inhibitors, knowledge of such rare adverse events is crucial. Evaluation of serum triglyceride levels before and after initiating pembrolizumab therapy may be mandated, especially in patients with metabolic comorbidities.

7.
Saudi Pharm J ; 32(5): 102048, 2024 May.
Article in English | MEDLINE | ID: mdl-38585197

ABSTRACT

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer's disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (-11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

8.
Proc (Bayl Univ Med Cent) ; 37(3): 437-447, 2024.
Article in English | MEDLINE | ID: mdl-38628340

ABSTRACT

Background: Acute pancreatitis (AP) is a complex and life-threatening disease. Early recognition of factors predicting morbidity and mortality is crucial. We aimed to develop and validate a pragmatic model to predict the individualized risk of early intensive care unit (ICU) admission for patients with AP. Methods: The 2019 Nationwide Readmission Database was used to identify patients hospitalized with a primary diagnosis of AP without ICU admission. A matched comparison cohort of AP patients with ICU admission within 7 days of hospitalization was identified from the National Inpatient Sample after 1:N propensity score matching. The least absolute shrinkage and selection operator (LASSO) regression was used to select predictors and develop an ICU acute pancreatitis risk (IAPR) score validated by 10-fold cross-validation. Results: A total of 1513 patients hospitalized for AP were included. The median age was 50.0 years (interquartile range: 39.0-63.0). The three predictors that were selected included hypoxia (area under the curve [AUC] 0.78), acute kidney injury (AUC 0.72), and cardiac arrhythmia (AUC 0.61). These variables were used to develop a nomogram that displayed excellent discrimination (AUC 0.874) (bootstrap bias-corrected 95% confidence interval 0.824-0.876). There was no evidence of miscalibration (test statistic = 2.88; P = 0.09). For high-risk patients (total score >6 points), the sensitivity was 68.94% and the specificity was 92.66%. Conclusions: This supervised machine learning-based model can help recognize high-risk AP hospitalizations. Clinicians may use the IAPR score to identify patients with AP at high risk of ICU admission within the first week of hospitalization.

9.
Plants (Basel) ; 13(6)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38592896

ABSTRACT

One of the most concerning global environmental issues is the pollution of agricultural soils by heavy metals (HMs), especially cadmium, which not only affects human health through Cd-containing foods but also impacts the quality of rice. The soil's nitrification and denitrification processes, coupled with the release of volatile organic compounds by plants, raise substantial concerns. In this review, we summarize the recent literature related to the deleterious effects of Cd on both soil processes related to the N cycle and rice quality, particularly aroma, in different water management practices. Under both continuous flooding (CF) and alternate wetting and drying (AWD) conditions, cadmium has been observed to reduce both the nitrification and denitrification processes. The adverse effects are more pronounced in alternate wetting and drying (AWD) as compared to continuous flooding (CF). Similarly, the alteration in rice aroma is more significant in AWD than in CF. The precise modulation of volatile organic compounds (VOCs) by Cd remains unclear based on the available literature. Nevertheless, HM accumulation is higher in AWD conditions compared to CF, leading to a detrimental impact on volatile organic compounds (VOCs). The literature concludes that AWD practices should be avoided in Cd-contaminated fields to decrease accumulation and maintain the quality of the rice. In the future, rhizospheric engineering and plant biotechnology can be used to decrease the transport of HMs from the soil to the plant's edible parts.

10.
Life Sci ; 345: 122613, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38582393

ABSTRACT

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.


Subject(s)
Brain Neoplasms , Glioblastoma , MicroRNAs , Humans , ErbB Receptors/metabolism , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Signal Transduction , MicroRNAs/metabolism , RNA, Untranslated/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism
11.
Chem Biol Interact ; 394: 111002, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38604395

ABSTRACT

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.


Subject(s)
Asthma , Bronchitis , Formaldehyde , Pulmonary Fibrosis , Formaldehyde/toxicity , Formaldehyde/adverse effects , Humans , Asthma/chemically induced , Pulmonary Fibrosis/chemically induced , Bronchitis/chemically induced , Animals , Environmental Exposure/adverse effects , Lung/drug effects , Lung/pathology , Pneumonia/chemically induced , Oxidative Stress/drug effects , Inflammation/chemically induced
12.
Sci Rep ; 14(1): 5751, 2024 03 08.
Article in English | MEDLINE | ID: mdl-38459108

ABSTRACT

L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC-MS and LC-MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N-H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm-1 to 5000 cm-1 respectively. GC-MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (- 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC-MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (- 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation.


Subject(s)
1-Butanol , Arthritis , Humans , Butanols , Spectroscopy, Fourier Transform Infrared , Antioxidants/chemistry , Anti-Bacterial Agents , Phytochemicals/pharmacology , Phytochemicals/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/analysis , Hypoglycemic Agents/pharmacology , Morphine Derivatives , Plant Extracts/chemistry
13.
Ann Med Surg (Lond) ; 86(3): 1483-1489, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38463085

ABSTRACT

The connection between cardiovascular illnesses and the gut microbiota has drawn more and more attention in recent years. According to research, there are intricate relationships between dietary elements, gut bacteria, and their metabolites that affect cardiovascular health. In this study, the role of gut microbiota in cardiovascular disorders is examined, with an emphasis on the cardiac consequences brought on by changes in gut microbiota. This essay discusses the gut-heart axis in depth and in detail. It talks about clinical research looking at how soy consumption, probiotic supplements, and dietary changes affected gut microbiota and cardiovascular risk variables. Our goal is to clarify the possible pathways that connect gut microbiota to cardiovascular health and the implications for upcoming treatment approaches. The authors examine the composition, roles, and effects of the gut microbiota on cardiovascular health, including their contributions to hypertension, atherosclerosis, lipid metabolism, and heart failure. Endotoxemia, inflammation, immunological dysfunction, and host lipid metabolism are some of the potential processes investigated for how the gut microbiota affects cardiac outcomes. The research emphasizes the need for larger interventional studies and personalized medicine strategies to completely understand the complexity of the gut-heart axis and its implications for the management of cardiovascular disease. The development of novel treatment strategies and cutting-edge diagnostic technologies in cardiovascular medicine may be facilitated by a better understanding of this axis.

14.
Cureus ; 16(2): e54069, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38481885

ABSTRACT

Arsenic is a natural element found in the earth's crust and is extensively present in various environmental components. Anthropogenic activities and a few natural events have generated contaminants that have led to massive environmental pollution, one form of which is arsenic contamination. Arsenic enters the human food chain via contaminated crops, water, seafood, and dairy products. In Pakistan, the increasing concentration of arsenic in the water is causing major health problems. Due to the serious health risks posed by arsenic, it is crucial to design and implement strategies for reducing and preventing the bioaccumulation of arsenic and its entry into the human food chain. There is a need for an institutional framework for arsenic mitigation, accountability, and systemic checks and balances. Targeted short- and long-term policies are required for effective and sustainable management.

15.
J Investig Med High Impact Case Rep ; 12: 23247096241238528, 2024.
Article in English | MEDLINE | ID: mdl-38491779

ABSTRACT

Lyme disease, caused by Borrelia burgdorferi and transmitted via Ixodes ticks, is a common vector-borne illness in the United States, with an estimated 476,000 annual cases. While primarily known for its neurological and rheumatological manifestations, Lyme disease can also involve the cardiac system, known as Lyme carditis, which occurs in about 4% to 10% of cases. This case report details a rare instance of Lyme carditis presenting as ST-segment elevation myocardial infarction (STEMI) in a 31-year-old female with no significant medical history. The patient exhibited symptoms of chest pressure and shortness of breath, with laboratory results showing significantly elevated troponin levels and other indicative markers. Notably, cardiac catheterization revealed no coronary occlusion, suggesting an alternative diagnosis to acute coronary syndrome (ACS). Further testing confirmed Lyme carditis through positive serological tests for Lyme-specific IgM antibodies. The case underscores the importance of considering Lyme myopericarditis in differential diagnoses for STEMI in Lyme-endemic areas and in patients without typical risk factors for coronary artery disease. This report aims to increase clinical awareness of this condition, highlighting the need for thorough investigation in atypical cardiac presentations.


Subject(s)
Acute Coronary Syndrome , Borrelia burgdorferi , Lyme Disease , Myocarditis , ST Elevation Myocardial Infarction , Female , Humans , United States , Adult , ST Elevation Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/complications , Myocarditis/diagnosis , Myocarditis/etiology , Lyme Disease/complications , Lyme Disease/diagnosis
16.
Pathol Res Pract ; 256: 155259, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38503004

ABSTRACT

Circular RNAs (circRNAs) have been recognized as key components in the intricate regulatory network of the KRAS pathway across various cancers. The KRAS pathway, a central signalling cascade crucial in tumorigenesis, has gained substantial emphasis as a possible therapeutic target. CircRNAs, a subgroup of non-coding RNAs known for their closed circular arrangement, play diverse roles in gene regulation, contributing to the intricate landscape of cancer biology. This review consolidates existing knowledge on circRNAs within the framework of the KRAS pathway, emphasizing their multifaceted functions in cancer progression. Notable circRNAs, such as Circ_GLG1 and circITGA7, have been identified as pivotal regulators in colorectal cancer (CRC), influencing KRAS expression and the Ras signaling pathway. Aside from their significance in gene regulation, circRNAs contribute to immune evasion, apoptosis, and drug tolerance within KRAS-driven cancers, adding complexity to the intricate interplay. While our comprehension of circRNAs in the KRAS pathway is evolving, challenges such as the diverse landscape of KRAS mutant tumors and the necessity for synergistic combination therapies persist. Integrating cutting-edge technologies, including deep learning-based prediction methods, holds the potential for unveiling disease-associated circRNAs and identifying novel therapeutic targets. Sustained research efforts are crucial to comprehensively unravel the molecular mechanisms governing the intricate interplay between circRNAs and the KRAS pathway, offering insights that could potentially revolutionize cancer diagnostics and treatment strategies.


Subject(s)
Neoplasms , RNA, Circular , Humans , RNA, Circular/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Neoplasms/genetics , Neoplastic Processes
17.
iScience ; 27(4): 109361, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38523776

ABSTRACT

Pakistan, among the top five most water-stressed nations globally, grapples with water scarcity owing to inadequate treatment infrastructure and groundwater overextraction. We demonstrate a successful nature-based closed-loop system to treat wastewater from urban vehicle-washing facilities, previously reliant on groundwater. An eco-friendly integrated system containing floating treatment wetlands (FTWs), subsurface flow constructed wetlands (SSF-CWs), and sand filtration (SF) was designed and installed at three vehicle-washing facilities for wastewater treatment and reuse in a loop. While the system is still operational after years, a consistent and significant reduction in water quality indicators is recorded, successfully meeting the national environmental quality standards of Pakistan. By reducing per unit water treatment costs to as low as $0.0163/m³ and achieving payback periods under a year, the embrace of these closed-loop strategies vividly underscores the imperative of transitioning to a circular economy in the domains of wastewater treatment and resource conservation.

18.
Nucl Med Mol Imaging ; 58(2): 95-96, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38510826

ABSTRACT

The technetium-99m methylene diphosphonate (99mTc-MDP) whole-body bone scan along with single-photon emission computed tomography (SPECT/CT) can detect challenging soft tissue uptake patterns. We present a case of a 67-year-old female in whom the 99mTc-MDP scan, performed 3 hours after injection, revealed abnormal soft tissue uptake in the right thoracic region. No functioning right kidney was seen in the right lumbar region. Hybrid SPECT/CT revealed an ectopic right kidney in the subdiaphragmatic location, accompanied by gut loops and eventration of the right-sided diaphragm. This case underscores the value of SPECT/CT in identifying and characterizing unexpected anatomical abnormalities, such as ectopic kidneys.

19.
Pathol Res Pract ; 256: 155224, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38452584

ABSTRACT

Sepsis, a potentially fatal illness caused by an improper host response to infection, remains a serious problem in the world of healthcare. In recent years, the role of ncRNA has emerged as a pivotal aspect in the intricate landscape of cellular regulation. The exploration of ncRNA-mediated regulatory networks reveals their profound influence on key molecular pathways orchestrating pyroptotic responses during septic conditions. Through a comprehensive analysis of current literature, we navigate the diverse classes of ncRNAs, including miRNAs, lncRNAs, and circRNAs, elucidating their roles as both facilitators and inhibitors in the modulation of pyroptotic processes. Furthermore, we highlight the potential diagnostic and therapeutic implications of targeting these ncRNAs in the context of sepsis, aiming to cover the method for novel and effective strategies to mitigate the devastating consequences of septic pathogenesis. As we unravel the complexities of this regulatory axis, a deeper understanding of the intricate crosstalk between ncRNAs and pyroptosis emerges, offering promising avenues for advancing our approach to sepsis intervention. The intricate pathophysiology of sepsis is examined in this review, which explores the dynamic interaction between ncRNAs and pyroptosis, a highly regulated kind of programmed cell death.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Sepsis , Humans , Pyroptosis/physiology , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , MicroRNAs/genetics , RNA, Long Noncoding/genetics
20.
Exp Gerontol ; 188: 112389, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432575

ABSTRACT

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the ß-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.


Subject(s)
Kaempferols , Respiratory Distress Syndrome , Humans , Kaempferols/pharmacology , Kaempferols/therapeutic use , Kaempferols/chemistry , Phosphatidylinositol 3-Kinases , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Aging , Respiratory Distress Syndrome/drug therapy
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