Recent Advances in Biosensor Technology for Early-Stage Detection of Hepatocellular Carcinoma-Specific Biomarkers: An Overview.

Hepatocellular carcinoma is currently the most common malignancy of the liver. It typically occurs due to a series of oncogenic mutations that lead to aberrant cell replication. Most commonly, hepatocellular carcinoma (HCC) occurs as a result of pre-occurring liver diseases, such as hepatitis and cirrhosis. Given its aggressive nature and poor prognosis, the early screening and diagnosis of HCC are crucial. However, due to its plethora of underlying risk factors and pathophysiologies, patient presentation often varies in the early stages, with many patients presenting with few, if any, specific symptoms in the early stages. Conventionally, screening and diagnosis are performed through radiological examination, with diagnosis confirmed by biopsy. Imaging modalities tend to be limited by their requirement of large, expensive equipment; time-consuming operation; and a lack of accurate diagnosis, whereas a biopsy's invasive nature makes it unappealing for repetitive use. Recently, biosensors have gained attention for their potential to detect numerous conditions rapidly, cheaply, accurately, and without complex equipment and training. Through their sensing platforms, they aim to detect various biomarkers, such as nucleic acids, proteins, and even whole cells extracted by a liquid biopsy. Numerous biosensors have been developed that may detect HCC in its early stages. We discuss the recent updates in biosensing technology, highlighting its competitive potential compared to conventional methodology and its prospects as a tool for screening and diagnosis.

Emerging role of exosomal microRNA in liver cancer in the era of precision medicine; potential and challenges.

Exosomal microRNAs (miRNAs) have great potential in the fight against hepatocellular carcinoma (HCC), the fourth most common cause of cancer-related death worldwide. In this study, we explored the various applications of these small molecules while analyzing their complex roles in tumor development, metastasis, and changes in the tumor microenvironment. We also discussed the complex interactions that exist between exosomal miRNAs and other non-coding RNAs such as circular RNAs, and show how these interactions coordinate important biochemical pathways that propel the development of HCC. The possibility of targeting exosomal miRNAs for therapeutic intervention is paramount, even beyond their mechanistic significance. We also highlighted their growing potential as cutting-edge biomarkers that could lead to tailored treatment plans by enabling early identification, precise prognosis, and real-time treatment response monitoring. This thorough analysis revealed an intricate network of exosomal miRNAs lead to HCC progression. Finally, strategies for purification and isolation of exosomes and advanced biosensing techniques for detection of exosomal miRNAs are also discussed. Overall, this comprehensive review sheds light on the complex web of exosomal miRNAs in HCC, offering valuable insights for future advancements in diagnosis, prognosis, and ultimately, improved outcomes for patients battling this deadly disease.

Blowflies (Diptera: Calliphoridae) as potential mechanical vectors of the protozoan cyst and helminthic eggs in Kashmir Himalaya, India.

Blowflies (Diptera: Calliphoridae) are an important group of non-biting flies that are potential mechanical vectors of protozoan and helminthic pathogens. The present study was carried out to isolate and identify protozoan cysts and helminthic eggs transmitted by blowflies. Surveys were carried out at six different sites, viz., butcher shops, fish markets, garbage piles, water bodies, and open vegetation in the Kashmir Himalaya. The flies were collected with the help of a sweeping net and using day-old beef liver as bait from March 2021 to February 2023. A total of 968 blowflies were collected, out of which 83 were found carrying at least one protozoan cyst and helminthic egg with six identified species of parasites. Garbage piles were recorded with the highest number of positive cases (10.81%), while human habitation had the highest transmission rate (3.3%). Chrysomya megacephala (Fabricius) was reported to have the highest number of parasitic cysts and ova (one protozoan cyst and three helminthic eggs), while Ascaris lumbricoides and Entamoeba coli were found to be the most abundant parasites reported from the surface of these flies. The number of parasites isolated from the surface of the blowflies was statistically significant (F = 9.073, df = 1, and p = 0.014), indicating a positive association between the number of parasites isolated from blowflies and the collection sites. Supplementary Information: The online version contains supplementary material available at 10.1007/s12639-024-01663-5.

Biosensing of Alpha-Fetoprotein: A Key Direction toward the Early Detection and Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges.

Hepatic cancer is widely regarded as the leading cause of cancer-related mortality worldwide. Despite recent advances in treatment options, the prognosis of liver cancer remains poor. Therefore, there is an urgent need to develop more representative in vitro models of liver cancer for pathophysiology and drug screening studies. Fortunately, an exciting new development for generating liver models in recent years has been the advent of organoid technology. Organoid models hold huge potential as an in vitro research tool because they can recapitulate the spatial architecture of primary liver cancers and maintain the molecular and functional variations of the native tissue counterparts during long-term culture in vitro. This review provides a comprehensive overview and discussion of the establishment and application of liver organoid models in vitro. Bioengineering strategies used to construct organoid models are also discussed. In addition, the clinical potential and other relevant applications of liver organoid models in different functional states are explored. In the end, this review discusses current limitations and future prospects to encourage further development.

Current status of indocyanine green fluorescent angiography in assessing perfusion of gastric conduit and oesophago-gastric anastomosis.

Anastomotic leak (AL) remains a significant complication after esophagectomy. Indocyanine green fluorescent angiography (ICG-FA) is a promising and safe technique for assessing gastric conduit (GC) perfusion intraoperatively. It provides detailed visualization of tissue perfusion and has demonstrated usefulness in oesophageal surgery. GC perfusion analysis by ICG-FA is crucial in constructing the conduit and selecting the anastomotic site and enables surgeons to make necessary adjustments during surgery to potentially reduce ALs. However, anastomotic integrity involves multiple factors, and ICG-FA must be combined with optimization of patient and procedural factors to decrease AL rates. This review summarizes ICG-FA's current applications in assessing esophago-gastric anastomosis perfusion, including qualitative and quantitative analysis and different imaging systems. It also explores how fluorescent imaging could decrease ALs and aid clinicians in utilizing ICG-FA to improve esophagectomy outcomes.

Emerging Biosensing Methods to Monitor Lung Cancer Biomarkers in Biological Samples: A Comprehensive Review.

Lung cancer is the most commonly diagnosed of all cancers and one of the leading causes of cancer deaths among men and women worldwide, causing 1.5 million deaths every year. Despite developments in cancer treatment technologies and new pharmaceutical products, high mortality and morbidity remain major challenges for researchers. More than 75% of lung cancer patients are diagnosed in advanced stages, leading to poor prognosis. Lung cancer is a multistep process associated with genetic and epigenetic abnormalities. Rapid, accurate, precise, and reliable detection of lung cancer biomarkers in biological fluids is essential for risk assessment for a given individual and mortality reduction. Traditional diagnostic tools are not sensitive enough to detect and diagnose lung cancer in the early stages. Therefore, the development of novel bioanalytical methods for early-stage screening and diagnosis is extremely important. Recently, biosensors have gained tremendous attention as an alternative to conventional methods because of their robustness, high sensitivity, inexpensiveness, and easy handling and deployment in point-of-care testing. This review provides an overview of the conventional methods currently used for lung cancer screening, classification, diagnosis, and prognosis, providing updates on research and developments in biosensor technology for the detection of lung cancer biomarkers in biological samples. Finally, it comments on recent advances and potential future challenges in the field of biosensors in the context of lung cancer diagnosis and point-of-care applications.

Lived experiences of women suffering from breast cancer in Kashmir: a phenomenological study.

Using a phenomenological approach, this study aimed to gain an in-depth understanding of the lived experiences of Kashmiri women suffering from breast cancer within the context of their day-to-day lives. Snowball sampling and theoretical sampling techniques were employed for recruiting participants. Data collection was primarily based on the principles of data saturation. Data saturation occurred after 12 women with breast cancer were interviewed. Data was collected using face-to-face in-depth individual interviews. The interview guide consisted of open-ended questions. To attain the utmost variation, sumptuousness and profundity of responses, interviewer asked probing, specific, and interpreting questions during interviews. Data analysis of the transcripts was based on Graneheim and Lundman's (Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse Education Today 2004;24:105-12) procedures for taking out themes in qualitative data. Two main themes emerged that explained the lived experiences of women with breast cancer: (i) challenges encountered (altered body image, embarrassment, perceived worries, financial constraints, dealing with negative attitudes and stigma) and (ii) coping strategies (reliance on religion and spirituality, social support, living as usual, optimistic attitude and will to recover, and venting out). The findings revealed that breast cancer diagnosis influences women significantly as they acknowledged that it wasthe most traumatic experience of their life; however, with time, they started to accept the reality and made use of various methods to cope with their illness.

Irinotecan inducing sinus pause bradycardia in a patient with small round cell cancer.

Irinotecan is a novel anticancer drug that has worked wonders in combination with other anticancer drugs. It can be used as a single chemotherapy agent in colonic cancer treatment or in combination with 5-fluorouracil. Irinotecan has been found a better salvage therapy in patients who are resistant to 5-fluorouracil. It is also used in combination with cisplatin and other drugs for cancers such as pleural mesothelioma, Ewing's sarcoma, lung cancer and others, and has helped reduce tumour burden. Irinotecan is generally associated with gastrointestinal side effects including nausea, vomiting and diarrhoea, while cardiovascular toxicity (5%) has been reported mainly as vasodilatation and possible bradycardia with no known incidence. A case was reported in 1998 by Miya et al of a 65-year-old man with bradycardia which was managed with atropine without modifications in the dosage of irinotecan or in the rate of infusion. We report a case of a patient with small round cell cancer who presented with sinus pause bradycardia after infusion with irinotecan. The patient was managed with atropine during chemotherapy.

Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis

ABSTRACT Objectives The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. Subjects and methods We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. Results Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. Conclusion Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

Rohitukine inhibits NF-κB activation induced by LPS and other inflammatory agents.

Rohitukine (referred to as RHK) is a bioactive chromone alkaloid isolated from the leaves of plant Dysoxylum binectariferum, which has been reported to possess diverse pharmacological properties for the treatment of inflammatory bowel disease (IBD), diarrhoea and anti-lipidemic. However, the underlying mechanism by which RHK exerts its anti-inflammatory activity has not yet demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of RHK using lipopolysaccharide (LPS) - stimulated J774A.1 macrophage cells and in-vivo inflammatory models. Results demonstrated that RHK treatment could significantly decrease the LPS-induced production of nitric oxide, prostaglandin E2 (PGE2), interleukins (ILs) and tumour necrosis factor (TNF)-α in J774A.1 cells. Molecular studies revealed that RHK inhibited the activation of upstream mediator nuclear factor-κB by suppressing the phosphorylation of IκBα and p65. In in-vivo experiments showed prominent anti-inflammatory activity of RHK. Thus, RHK could be considered as a promising candidate for the treatment of inflammatory diseases.

Tunneling Nanotubes and Gap Junctions-Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions.

Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described tunneling nanotubes (TNTs). It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.

Two-Dimensional Surface Plasmon Resonance Imaging System for Cellular Analysis.

Optical biosensors based on surface plasmon resonance (SPR) phenomenon have received a great deal of attention in cellular analysis applications. Sensitive and high-resolution SPR imaging (SPRi) platforms are very useful for real-time monitoring and measurement of individual cell responses to various exogenous substances. In cellular analysis, mainstream SPR-based sensors have potential for investigations of cell responses under ambient conditions. Evaluations that account only for the average response of cell monolayers mask the understanding of precise cell-molecular interactions or intracellular reactions at the level of individual cells. SPR/SPRi technology has attracted a great deal of attention for detecting the response of cell monolayers to various substances cultivated on the gold sensor chip. To unleash the full strength of SPRi technology in complex cell bio-systems, the applied SPR imaging system needs to be sufficiently effective to allow evaluation of a compound's potency, specificity, selectivity, toxicity, and effectiveness at the level of the individual cell. In our studies, we explore the utility of high-resolution 2D-SPR imaging for real-time monitoring of intracellular translocation of protein kinase C (PKC), and detection of neuronal differentiation in live cells at the level of individual cells. The PC12 cell line, which is one of the most commonly used neuronal precursor cell lines for research on neuronal differentiation, was chosen as a nerve cell model. Two dimensional SPR (2D-SPR) signals/images are successfully generated. We have found that cells treated with the differentiation factor nerve growth factor (NGF) showed a remarkable enhancement of SPR response to stimulation by muscarine, a nonselective agonist of the muscarinic acetylcholine receptor.

Amperometric sensing of HIF1α expressed in cancer cells and the effect of hypoxic mimicking agents.

Hypoxia inducible factor 1 alpha (HIF1α) overexpression was detected in cancerous cells using an amperometric immunosensor with a nano-bioconjugate. The sensor probe was fabricated by covalently immobilizing the antibody (anti-HIF1α) onto a composite layer of functionalized conducting polymer [2,2:5,2-terthiophene-3-(p-benzoic acid)] (pTTBA) formed on a layer of gold nanoparticles (AuNPs). A nano-bioconjugate with hydrazine and a secondary antibody of HIF1α (sec-Ab2) attached on AuNPs reveals the immunoreaction at the sensor probe through the catalytic reduction of H2O2 by hydrazine at -0.35V vs. Ag/AgCl. Morphology and performance of the sensor probe were characterized using FE-SEM, XPS, EIS, and cyclic voltammetry. The calibration plot at optimized experimental conditions shows a dynamic range of 25-350pM/mL with a detection limit of 5.35±0.02pM/mL. The reliability of the sensor was evaluated using non-cancerous Vero and cancerous MCF-7 cell lysates, where the HIF1α expression was compared with three cancerous cell lines MCF-7, PC-3, and A549. Furthermore, the sensor probe confirms the stable expression of HIF1α in the A549 lung cancer cells when exposing them to hypoxic mimicking agents Co, Ni, and Mn ions. Of these, Co ions show the highest stabilization effect on HIF1α followed by Ni and Mn ions, respectively.

An amperometric nanobiosensor for the selective detection of K⁺-induced dopamine released from living cells.

A highly sensitive amperometric sensor has been studied for selective monitoring of K(+)-induced dopamine released from dopaminergic cells (PC12) which is based on an EDTA immobilized-poly(1,5-diaminonaphthalne) (poly-DAN) layer comprising graphene oxide (GO) and gold nanoparticles (GO/AuNPs). The integration of a negatively charged probe molecule on the poly-DAN/GO/AuNPs nanohybrid attained the signal enhancement to discriminate dopamine (DA) molecules from foreign species by catalytic effect and surface charge, and hydrogen bonding-based interactions with a probe molecule. The sensor performance and morphology were investigated using voltammetry, impedance spectrometry, SEM, and XPS. Experimental variables affecting the analytical performance of the sensor probe were optimized, and linear response was observed in the range of 10 nM-1 µM with a detection limit of 5.0 nM (±0.01) for DA. Then, the sensor was applied to monitor dopamine released from PC12 cells upon extracellular stimulation of K(+) ions. It was also confirmed that K(+)-induced dopamine release was inhibited by a calcium channel inhibitor (Nifidipine). The results demonstrated that the presented biosensor could be used as an excellent tool for monitoring the effect of exogenous agents on living cells and drug efficacy tests.

A preliminary investigation of chitosan film as dressing for punch biopsy wounds in rats.

PURPOSE: To investigate the wound healing efficacy of two chitosan films, Chit-AA and Chit-LA, in comparison with a commercial preparation, Omiderm, using punch biopsy wounds in rats. METHODS: The punch biopsy wounds were created in the abdominal region of male Wistar rats. The films were evaluated in terms of transparency, flexibility, adherence property, ease of removal from wounds without damaging underlying tissues and fluid accumulation. In addition, the wounds were examined for dryness, exudation, contraction, period of epithelialization and scar formation. RESULTS: Chit-AA, Chit-LA and Omiderm films were comparable in terms of transparency, flexibility, adherence property, ease of film removal from wounds without damaging underlying tissues and fluid accumulation. Although there was no statistically significant difference in wound dryness and exudation between the film treated wounds and untreated wounds (Control), a significant difference was obtained in complete wound closure (t(100%)), period of epithelialization and scar formation. CONCLUSIONS: Both Chit-LA and Chit-AA were able to promote wound healing with minimal scar formation.