Breast cancer derived exosomes: Theragnostic perspectives and implications.

Breast cancer (BC) is the most prevalent malignancy affecting women worldwide. Although conventional treatments such as chemotherapy, surgery, hormone therapy, radiation therapy, and biological therapy are commonly used, they often entail significant side effects. Therefore, there is a critical need to investigate more cost-effective and efficient treatment modalities in BC. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, play a crucial role in modulating recipient cell behaviour and driving cancer progression. Among the EVs, exosomes provide valuable insights into cellular dynamics under both healthy and diseased conditions. In cancer, exosomes play a critical role in driving tumor progression and facilitating the development of drug resistance. BC-derived exosomes (BCex) dynamically influence BC progression by regulating cell proliferation, immunosuppression, angiogenesis, metastasis, and the development of treatment resistance. Additionally, BCex serve as promising diagnostic markers in BC which are detectable in bodily fluids such as urine and saliva. Targeted manipulation of BCex holds significant therapeutic potential. This review explores the therapeutic and diagnostic implications of exosomes in BC, underscoring their relevance to the disease. Furthermore, it discusses future directions for exosome-based research in BC, emphasizing the necessity for further exploration in this area.

Piceatannol improved cerebral blood flow and attenuated JNK3 and mitochondrial apoptotic pathway in a global ischemic model to produce neuroprotection.

Cerebral ischemia is one of the leading causes of death and disability worldwide. The only FDA-approved treatment is recanalization with systemic tissue plasminogen activators like alteplase, although reperfusion caused by recanalization can result in neuroinflammation, which can cause brain cell apoptosis. Therefore, after an ischemic/reperfusion injury, interventions are needed to minimize the neuroinflammatory cascade. In the present study, piceatannol (PCT) was studied for its neuroprotective efficacy in a rat model of global ischemic injury by attenuating c-Jun N-terminal kinase 3 (JNK3) downstream signaling. PCT is a resveratrol analog and a polyphenolic stilbenoid naturally occurring in passion fruit and grapes. The neuroprotective efficacy of PCT (1, 5, 10 mg/kg) in ischemic conditions was assessed through pre- and post-treatment. Cerebral blood flow (CBF) and tests for functional recovery were assessed. Protein and gene expression were done for JNK3 and other inflammatory markers. A docking study was performed to identify the amino acid interaction. The results showed that PCT improved motor and memory function as measured by a functional recovery test believed to be due to an increase in cerebral blood flow. Also, the caspase signaling which promotes apoptosis was found to be down-regulated; however, nitric oxide synthase expression was up-regulated, which could explain the enhanced cerebral blood flow (CBF). According to our findings, PCT impeded c-Jun N-terminal kinase 3 (JNK3) signaling by suppressing phosphorylation and disrupting the mitochondrial apoptotic pathway, which resulted in the neuroprotective effect. Molecular docking analysis was performed to investigate the atomic-level interaction of JNK3 and PCT, which reveals that Met149, Leu206, and Lys93 amino acid residues are critical for the interaction of PCT and JNK3. According to our current research, JNK3 downstream signaling and the mitochondrial apoptosis pathway are both inhibited by PCT, which results in neuroprotection under conditions of global brain ischemia. Piceatannol attenuated JNK3 phosphorylation during the ischemic condition and prevented neuronal apoptosis.

The Utility of Methylphenidate for Fatigue in Long-Term Neurological Conditions: A Meta-analytical Review.

OBJECTIVE: Fatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in other clinical groups, little work has explored its potential utility within LTNCs. The current systematic review and meta-analysis evaluates the utility of methylphenidate for symptoms of fatigue in LTNCs. METHODS: Five databases (PsycINFO, MEDLINE, Embase, Scopus, and Cochrane Library) were searched for relevant articles from their inception to February 2022. A purpose-developed evaluation tool was used to assess each study's research quality (QuEST:F). RESULTS: Of the 1698 articles identified, 11 articles were included within this review (n = 370). Meta-analytical findings reported an overall significant benefit of methylphenidate for symptoms of fatigue across a mixed neurological sample ( g = -0.44; 95% confidence interval, -0.77 to -0.11). Subgroup analyses identified a significantly greater benefit ( P < 0.001) of methylphenidate for fatigue in LTNCs with static pathogenic trajectories (eg, traumatic brain injury) (number needed to treat = 2.5) compared with progressive conditions (eg, multiple sclerosis) (number needed to treat = 40.2). CONCLUSIONS: Methylphenidate may pose an effective intervention for the treatment of fatigue in a number of LTNCs. Nonetheless, given the quality of the current evidence base, there exists a clear need for further robust assessment of the utility of methylphenidate-with a focus on subgroup-specific variability.

Biomechanical analysis of a single-level customized cage screw fixation for anterior cervical discectomy and fusion in the cervical spine: anin-silicostudy.

The usual surgical choice of customized cage fixation is anterior cervical discectomy and fusion (ACDF) for cervical spondylosis with disc herniation. The safe and successful cage fixation for ACDF surgery benefits patients with cervical disc degenerative disease by easing their discomfort and regaining function. The cage prevents mobility between the vertebrae by using cage fixation to anchor the neighbouring vertebrae. The goal of the current study is to develop a customized cage-screw implant for single-level cage fixation at C4-C5 level of the cervical spine (C2-C7). The Finite Element Analysis (FEA) is performed for the intact and implanted cervical spine and analysed the flexibility, stress of the implant and implant adjacent bone during three physiological loading conditions being analysed. Lower surface of the C7 vertebrae is fixed and 50 N compressive force with 1 Nm moment are applied on the C2 vertebrae for simulated lateral bending, axial rotation and flexion-extension. The flexibility is decreased at single level of fixation (C4-C5 level) by 64% to 86%, as compared to natural cervical spine. The flexibility is increased 3% to 17% at the nearest levels of fixation. The maximum Von Mises stress in PEEK cage varies from 24 to 59 MPa and for Ti-6Al-4V screw the stress varies from 84 MPa to 121 MPa which are far below the yield stress of PEEK (95 MPa) and Ti-6Al-4V (750 MPa).

Prevalence of dysphagia following posterior fossa tumour resection in children: the Alder Hey experience.

BACKGROUND: Surgery for posterior fossa tumours (PFTs) in children is associated with bulbar palsy and swallowing difficulties although this risk is not well defined in the literature and issues contributing to dysphagia following surgery are not fully understood. AIMS: This study aims to study the eating, drinking and swallowing function of children following PFT resection in a specialist paediatric neurosurgery centre. This included the frequency and duration of dysphagia, the risk of aspiration and the link between tumour type and dysphagia. MATERIALS AND METHODS: This is a retrospective review of children undergoing surgery for PFT between 2014 and 2019. Information was obtained from the patients' hospital and speech and language therapy (SLT) notes, oncology database and clinical letters. The International Dysphagia Diet Standardisation Initiative (IDDSI) Framework was used to describe food and fluid modifications. RESULTS: Seventy children had surgery to resect a posterior fossa tumour at Alder Hey from 2014 to 2019. Thirty-one children were included in the study following referral to SLT. Videofluoroscopy (VF) was undertaken at our institution in 68% (21/31) of cases. Fifty-two percent (11/21) of children aspirated or were considered at risk, and 55% (6/11) of those who aspirated showed silent aspiration. After 3 months, 43% (13/30) still required modified food and/or fluid textures, with this proportion reducing as time progressed. By tumour type, VF was performed in 5/7 medulloblastoma patients with 3/5 showing aspiration and 3/3 silently aspirating; in 8/9 patients with ependymoma with 4/8 patients aspirating with 2/4 showing silent aspiration; and 6/12 glioma patients with 4/6 aspirating with 1/4 showing silent aspiration. CONCLUSION: Swallowing difficulties, including silent aspiration, are an important complication of PFT resection. A proportion of children will need ongoing food and/or fluid modification. Further study into dysphagia following PFT resection is indicated.

Comparative evaluation of the efficacy of Nigella sativa (75% v/v) cream and clobetasol propionate (0.05% w/w) gel in oral lichen planus-a double-blinded randomized control trial.

OBJECTIVES: The a im of this study is to evaluate and compare the efficacy of Nigella sativa (75% v/v) cream and clobetasol propionate (0.05% w/w) gel for the management of oral lichen planus (OLP). STUDY DESIGN: Sixty clinically diagnosed cases of OLP were stratified into moderate cases or severe cases based on burning sensation before getting allocated to group I receiving Nigella sativa cream and group II receiving clobetasol propionate gel, two times a day for 45 days. Patients were examined every 15 days for a change in burning sensation and size of the lesion using the numeric pain rating scale (NRS) and a standard Vernier caliper, respectively. Statistical tests including Mann-Whitney U, Wilcoxon signed-rank, Friedman's, Dunn's post hoc, unpaired t, paired t, one-way repeated measures ANOVA, and Bonferroni's post hoc were applied. RESULTS: There was a statistically significant reduction in the burning sensation as well as the size of the lesion in both groups (P ≤ 0.05). There was an 87.8% (moderate cases) and 85.7% (severe cases) reduction in the mean NRS scores on the 45th day in group I when compared to the 96.5% (moderate cases) and 93.48% (severe cases) in group II. There was a 92.9% (moderate cases) and 90.7% (severe cases) reduction in the size of the lesion in group I when compared to the 92.6% (moderate cases) and 93.1% (severe cases) in group II. CONCLUSION: The topical application of Nigella sativa cream was effective and comparable to clobetasol propionate 0.05% gel in the management of OLP, without any side effects. Hence, this study recommends the use of topical Nigella sativa cream therapy in the management of OLP. CLINICAL RELEVANCE: The current mainstay of treatment for OLP is the administration of topical or systemic corticosteroids, which are known to cause side effects, demanding a search for an alternative. Nigella sativa oil cream could be a safe, promising, cost-effective, adjunctive, or alternative modality. Clinical trial registration number: CTRI/2020/07/026745 (India).

Selection and Validation of the Most Suitable Reference Genes for Quantitative Real-Time PCR Normalization in Salvia rosmarinus under In Vitro Conditions.

Salvia rosmarinus L. (rosemary) is known to have a wide range of pharmacological effects including antidiabetic, anticarcinogenic, and antitumorigenic properties owing to its secondary metabolites. Studies aiming to elevate these metabolites have utilized various elicitors and stresses under in vitro conditions, although underlying molecular mechanisms remain unexplored. Gene expression studies using RT-qPCR might provide valuable information regarding how plant and plant cells interact and perceive various treatments and elicitors. However, despite being able to calculate accurate fold changes, the accuracy of the RT-qPCR data highly depends on the expression of reference genes. To the best of our knowledge, there is no information available on the stable reference genes in rosemary under in vitro conditions. Thus, in this paper, we assessed the stability of seven commonly used reference genes under different elicitor and stress conditions using RT-qPCR. Thereafter, the five most commonly used software and algorithms (comparative ΔCt, BestKeeper, NormFinder, geNorm, and RefFinder) were used to rank the candidates based on their expression stabilities. In conclusion, we recommend using a combination of F1-ATPase, ATP synthase and ACCase to normalize the gene expression experiments in rosemary under in vitro conditions. The selected reference genes were verified using 4-coumarate-CoA ligase, a pharmacologically important gene, whose expression might alter under nanoparticle treatment. Additionally, reference genes for several plant tissues, elicitors, and stresses are also proposed. The conclusions obtained from this current study will accelerate the future molecular work in S. rosmarinus and other related species.

Mycobacterium tuberculosis ketol-acid reductoisomerase down-regulation affects its ability to persist, and its survival in macrophages and in mice.

Branched-chain amino acids (BCAAs) leucine, isoleucine and valine biosynthetic pathways have been reported from plants, fungi and bacteria including Mycobacterium tuberculosis (Mtb) but are absent in animals. This makes interventions with BCAAs biosynthesis an attractive proposition for antimycobacterial drug discovery. In the present study, Mycobacterium tuberculosis H37Ra (Mtb-Ra) ketol-acid reductoisomerase encoding ORF MRA_3031 was studied to establish its role in Mtb-Ra growth and survival. Recombinant knockdown (KD) and complemented (KDC) strains along with wild-type (WT) Mtb-Ra were studied under in-vitro and ex-vivo conditions. KD was defective for survival inside macrophages and showed time dependent decrease in its colony forming unit (CFU) counts, while, WT and KDC showed time dependent increase in CFUs, after macrophage infection. Also, KD showed reduced ability to form persister cells, had altered membrane permeability against ethidium bromide and nile red dyes, and had reduced biofilm maturation, compared to WT and KDC. The in-vivo studies showed that KD infected mice had lower CFU counts in lungs, compared to WT. In summary Mtb shows survival deficit in macrophages and in mice after ketol-acid reductoisomerase down-regulation.

Comparison of changes in endothelial cell count and central corneal thickness after phacoemulsification and small-incision cataract surgery: A prospective observational study at a tertiary care center of eastern Uttar Pradesh.

Purpose: Morphological stability and functional integrity of corneal endothelium are necessary to maintain long-term corneal transparency. When the number of endothelial cells drops below 450-800 cells/mm2, corneal edema, irreversible loss of corneal transparency, and decreased vision occur. There is concern regarding manual small-incision cataract surgery (MSICS) being more harmful to the endothelium in comparison to phacoemulsification. Our study aims to determine which technique maintains the corneal parameters closest to the normal physiological state. Methods: A prospective observational study was conducted over a period of 15 months on 100 eyes, out of which 43 patients underwent phacoemulsification surgery and 57 underwent MSICS. TOPCON SP-1P, Version 1.41, 50-60 Hz frequency, noncontact specular microscope with pachymeter was used to measure endothelial cell count (ECC) and central corneal thickness (CCT) on four occasions: 1 day prior to surgery and on day 1, 3rd week, and 6th week after surgery. Results: In total, 100 eyes of 100 subjects were studied with no dropout during the study period. The age range was 40-70 years. There was no statistically significant difference between the preoperative mean ECC and mean CCT in phacoemulsification and SICS groups. A statistically significant difference was observed in the postoperative mean ECC (P < 0.01) and mean CCT (P < 0.001) on day 1 and 3rd week between the phacoemulsification and SICS groups, respectively. The mean endothelial cell loss at 6 weeks was less with SICS but comparable with phacoemulsification. Conclusion: SICS is significantly faster, less expensive, less technology dependent, can deal with all types of cataracts, is relatively safe, and is more appropriate for advanced cataracts.

Bioactive Flavonoids: A Comprehensive Review on Pharmacokinetics and Analytical Aspects.

Flavonoids are a diversified group of natural substances which were discovered to provide a variety of health benefits in human beings. Vegetables, fruits, wine and tea are the primary flavonoid dietary sources for humans and as the flavonoids are so closely connected to human dietary items and health, it is vital to explore the structural-activity connection. The arrangement, replacement of functional groups, and total number of hydroxyl groups around flavonoid's nucleus structure affect their biological activity, metabolism, and bioavailability. Various flavonoids have been proven to have hepatoprotective properties, that help in the prevention of coronary heart disease. Similarly, these flavonoids also possess anticancer, and anti-inflammatory activities. Flavonoids have been found to have a functional and structural link with their enzyme inhibitory action, that appears to have antiviral effect through acting as antioxidants, damaging cell membranes, blocking enzymes, activating mechanisms of host self-defense, and limiting virus penetration and attaching to cells. Identification, characterization, isolation, and biological role of flavonoids, as well as their uses on health advantages, are all major topics in research and development currently. This review represents a summary of various sources of flavonoids, class, subclass, their chemical structures, biological activities, the pharmacokinetics of flavonoids and various analytical, bioanalytical and electrochemical methods for determination of flavonoids from different matrices.

SegNet and Salp Water Optimization-driven Deep Belief Network for Segmentation and Classification of Brain Tumor.

Classification of brain tumor in Magnetic Resonance Imaging (MRI) images is highly popular in treatment planning, early diagnosis, and outcome evaluation. It is very difficult for classifying and diagnosing tumors from several images. Thus, an automatic prediction strategy is essential in classifying brain tumors as malignant, core, edema, or benign. In this research, a novel approach using Salp Water Optimization-based Deep Belief network (SWO-based DBN) is introduced to classify brain tumor. At the initial stage, the input image is pre-processed to eradicate the artifacts present in input image. Following pre-processing, the segmentation is executed by SegNet, where the SegNet is trained using the proposed SWO. Moreover, the Convolutional Neural Network (CNN) features are employed to mine the features for future processing. At last, the introduced SWO-based DBN technique efficiently categorizes the brain tumor with respect to the extracted features. Thereafter, the produced output of the introduced SegNet + SWO-based DBN is made use of in brain tumor segmentation and classification. The developed technique produced better results with highest values of accuracy at 0.933, specificity at 0.880, and sensitivity at 0.938 using BRATS, 2018 datasets and accuracy at 0.921, specificity at 0.853, and sensitivity at 0.928 for BRATS, 2020 dataset.

Idiopathic intracranial hypertension in children with obesity.

AIM: Obesity is an under-recognised risk factor for raised intracranial pressure in the paediatric population. The pathophysiology remains unclear. The aim of our study was to investigate the association between idiopathic intracranial hypertension (IIH) and weight in children. METHODS: Patients diagnosed with IIH at a tertiary children's hospital were retrospectively identified between April 2017 and April 2019. Information regarding the patients' body mass index, presentation, investigation and treatment was collected and analysed. RESULTS: In total, 18 patients (M:F 7:11) were identified with a mean age of 11 years (±3.3SD; range: 6-15 years). The mean BMI was 30.3 kg/m2 and mean BMI SDS was +2.5. Twelve (66.6%) patients presented with both headaches and eye signs. Three patients were asymptomatic, with papilloedema noted on routine optician review. Of the 18 patients, 15 were treated medically, two had long-term neurosurgical interventions and one patient was managed conservatively. CONCLUSION: The results show that the majority of children with obesity who develop IIH were female. Awareness regarding IIH secondary to obesity needs to be highlighted to ensure detailed clinical evaluation takes place so that raised intracranial pressure can be diagnosed and managed earlier, to avoid more serious complications such as permanent visual loss.

Basilar Artery Vasospasm as a Cause of Post-Operative Cerebellar Mutism Syndrome.

Post-operative cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome (PFS), is a well-recognized and frequent complication of surgery for posterior fossa tumours in children and young people. Its incidence varies between 8 and 31%, and the pathophysiological mechanisms of delayed onset and resolution of cerebellar mutism are not clear, but axonal damage, oedema, and perfusion defects may be involved. Magnetic resonance imaging has failed to reveal a universal anatomical substrate or a single definite mechanism of injury. We present a case of 16-year-old boy who developed CMS three days after resection of a medulloblastoma, a primary fourth ventricular tumour. Early post-operative imaging showed bleeding in the posterior fossa which required evacuation. CT angiography seven days after surgery demonstrated basilar artery vasospasm. Magnetic resonance brain angiography confirmed persistent narrowing of a segment of the basilar artery closely related to a left cerebellopontine (CP) angle peri-operative haematoma. The patient was treated with nimodipine and hypervolemia. The patient started vocalisation without speech five days later with reversal of radiological lesions. Further recovery of post-operative neurological deficits occurred over a protracted period of several months. This case represents a rare cause of post-operative CMS, with rapid initial recovery that occurred after specific treatment directed at the cause. To our knowledge, this is the first reported case showing mutism associated with basilar artery vasospasm with imaging evidence. This case may suggest the need to undertake urgent vascular imaging in selected cases of post-operative CMS.

Modulation of BRCA1 mediated DNA damage repair by deregulated ER-α signaling in breast cancers.

BRCA1 mutation carriers have a greater risk of developing cancers in hormone-responsive tissues like breasts and ovaries. However, this tissue-specific incidence of BRCA1 related cancers remains elusive. The majority of the BRCA1 mutated breast cancers exhibit typical histopathological features of high-grade tumors, with basal epithelial phenotype, classified as triple-negative molecular subtype and have a higher percentage of DNA damage and chromosomal abnormality. Though there are many studies relating BRCA1 with ER-α (Estrogen receptor-α), it has not been reported whether E2 (Estrogen) -ER-α signaling can modulate the DNA repair activities of BRCA1. The present study analyzes whether deregulation of ER-α signaling, arising as a result of E2/ER-α deficiency, could impact the BRCA1 dependent DDR (DNA Damage Response) pathways, predominantly those of DNA-DSB (Double Strand break) repair and oxidative damage response. We demonstrate that E2/E2-stimulated ER-α can augment BRCA1 mediated high fidelity repairs like HRR (Homologous Recombination Repair) and BER (Base Excision Repair) in breast cancer cells. Conversely, a condition of ER-α deficiency itself or any interruption in ligand-dependent ER-α transactivation resulted in delayed DNA damage repair, leading to persistent activation of γH2AX and retention of unrepaired DNA lesions, thereby triggering tumor progression. ER-α deficiency not only limited the HRR in cells but also facilitated the DSB repair through error prone pathways like NHEJ (Non Homologous End Joining). ER-α deficiency associated persistence of DNA lesions and reduced expression of DDR proteins were validated in human mammary tumors.

Role of Serum Interleukin-6 and C-reactive Protein in Early Prediction of Severe Acute Pancreatitis.

Background: Early prediction of severity is an important goal in acute pancreatitis (AP), to identify 20% of patients who are likely to have a severe course. Such patients have an expected mortality of 15-20% and may benefit from early admission to high dependency or intensive care units, with parenteral or nasojejunal feeding and prophylactic antibiotics. In severe AP (SAP), multiorgan dysfunction accounts for most of early deaths. Aims: The aim of this article is to assess the role of serum interleukin (IL)-6 and serum C-reactive protein (CRP) in early prediction of severity of AP. Materials and Methods: This observational analytical study was conducted in the Department of General Surgery and Department of Biochemistry in our hospital in 62 patients as per inclusion and exclusion criteria. Results: IL-6 on day 1 and day 2 as well as CRP on day 2 was 100% sensitive but IL-6 on day 1 and day 2 had a maximum specificity of 88.37% among them when compared with a specificity of 81.4% of CRP on day 2. Though CRP on day 1 also had a specificity of 88.37%, its sensitivity was 89.47%. Conclusion: IL-6 and CRP together appear to be a promising marker for assessing the severity of AP within 48 h. We recommend to do IL-6 and CRP in patients with AP, which can help in predicting severity of the disease in patients.

S-adenosylmethionine-dependent methyltransferase inhibitor DZNep blocks transcription and translation of SARS-CoV-2 genome with a low tendency to select for drug-resistant viral variants.

We report the in vitro antiviral activity of DZNep (3-Deazaneplanocin A; an inhibitor of S-adenosylmethionine-dependent methyltransferase) against SARS-CoV-2, besides demonstrating its protective efficacy against lethal infection of infectious bronchitis virus (IBV, a member of the Coronaviridae family). DZNep treatment resulted in reduced synthesis of SARS-CoV-2 RNA and proteins without affecting other steps of viral life cycle. We demonstrated that deposition of N6-methyl adenosine (m6A) in SARS-CoV-2 RNA in the infected cells recruits heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), an RNA binding protein which serves as a m6A reader. DZNep inhibited the recruitment of hnRNPA1 at m6A-modified SARS-CoV-2 RNA which eventually suppressed the synthesis of the viral genome. In addition, m6A-marked RNA and hnRNPA1 interaction was also shown to regulate early translation to replication switch of SARS-CoV-2 genome. Furthermore, abrogation of methylation by DZNep also resulted in defective synthesis of the 5' cap of viral RNA, thereby resulting in its failure to interact with eIF4E (a cap-binding protein), eventually leading to a decreased synthesis of viral proteins. Most importantly, DZNep-resistant mutants could not be observed upon long-term sequential passage of SARS-CoV-2 in cell culture. In summary, we report the novel role of methylation in the life cycle of SARS-CoV-2 and propose that targeting the methylome using DZNep could be of significant therapeutic value against SARS-CoV-2 infection.

Advancement of Scaffold-Based 3D Cellular Models in Cancer Tissue Engineering: An Update.

The lack of traditional cancer treatments has resulted in an increased need for new clinical techniques. Standard two-dimensional (2D) models used to validate drug efficacy and screening have a low in vitro-in vivo translation potential. Recreating the in vivo tumor microenvironment at the three-dimensional (3D) level is essential to resolve these limitations in the 2D culture and improve therapy results. The physical and mechanical environments of 3D culture allow cancer cells to expand in a heterogeneous manner, adopt different phenotypes, gene and protein profiles, and develop metastatic potential and drug resistance similar to human tumors. The current application of 3D scaffold culture systems based on synthetic polymers or selected extracellular matrix components promotes signalling, survival, and cancer cell proliferation. This review will focus on the recent advancement of numerous 3D-based scaffold models for cancer tissue engineering, which will increase the predictive ability of preclinical studies and significantly improve clinical translation.

Gonadotropin inhibitory hormone receptors (GnIHRs): Molecular characterization and synergistic effect of different drugs in Indian major carp, Labeo catla.

After the discovery of Gonadotropin-inhibitory hormone (GnIH) in birds in 2000, it showed different roles in different vertebrate classes and even in different species of same classes. In birds and mammals, GnIH inhibits the expression of gonadotropins during reproduction, while in fishes it exerts both inhibitory and stimulatory effect on reproduction. The current study evaluates the role of GnIH during reproduction in Labeo catla. The partial cDNA sequence of GnIHR1 and GnIHR3 receptor genes was identified by degenerate PCR. The mRNA expression analysis of GnIHRs during different reproductive phases showed that the expression of all three GnIH receptor genes is highest during spawning phase. The expression of GnIH receptors is detected in both brain and gonads except for GnIHR3 which only expressed in gonads. The in vivo experiments with GnIH antagonist, RF313 drastically reduced the expression level of reproduction related genes like LH, FSH, and GnRH at 1 h post-injection. In another experiment the surge induced by cGnIH-III peptide on gonadotropins gene expression is further increased when co-injected with LHRHa. However, co-injection of melatonin along with cGnIH-III peptide had opposite effects. These results showed that the GnIH/GnIHRs system has positive effect on reproduction in L. catla.