Anti-pruritic effect of L-carnitine against chloroquine-induced pruritus mediated via nitric oxide pathway.

BACKGROUND: Pruritus, or itching, is a distressing symptom associated with various dermatological and systemic diseases. L-carnitine (ßeta hydroxy-γ-tri methyl amino-butyric acid), is a naturally occurring substance, it controls numerous physiological processes. The present research aims to identify L-carnitine for its anti-pruritic effect via nitric oxide-dependent mechanism. METHODS: Chloroquine-induced pruritus serves as an experimental model to investigate possible therapeutic interventions. In this study, we evaluated the efficacy of L-carnitine in combating oxidative stress, nitric oxide, and inflammatory cytokines in a chloroquine-induced pruritus model. RESULTS: L-carnitine treatment significantly reduced scratching behavior compared to the disease group (***P < 0.001 vs. chloroquine group), indicating its antipruritic potential. The markers of oxidative stress, GST, GSH, Catalase, and LPO were dysregulated in the disease model, but administration of L-carnitine restored GST, GSH, and Catalase levels and decreased LPO levels (***P < 0.001 vs. chloroquine group), thereby alleviating oxidative stress. L-carnitine also reduced nitric oxide synthase (NOS) activity, suggesting that it modulates nitric oxide signaling pathways involved in pruritus. In addition, L-carnitine lowered levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), inflammatory marker nuclear factor kappa B (p-NFκB) and also reduces an inflammatory enzyme, cyclooxygenase-2 (COX-2), determined by ELISA (Enzyme-Linked Immunosorbent Assay) (***P < 0.001 vs. chloroquine group). It downregulates nNOS mRNA expression confirmed by real-time polymerase chain reaction (RT-PCR). CONCLUSION: These findings highlight the therapeutic effects of L-carnitine in alleviating chloroquine-induced pruritus.

Updated review on analysis of long non-coding RNAs as emerging diagnostic and therapeutic targets in prostate cancers.

Despite advancements, prostate cancers (PCa) pose a significant global health challenge due to delayed diagnosis and therapeutic resistance. This review delves into the complex landscape of prostate cancer, with a focus on long-noncoding RNAs (lncRNAs). Also explores the influence of aberrant lncRNAs expression in progressive PCa stages, impacting traits like proliferation, invasion, metastasis and therapeutic resistance. The study elucidates how lncRNAs modulate crucial molecular effectors, including transcription factors and microRNAs, affecting signaling pathways such as androgen receptor signaling. Besides, this manuscript sheds light on novel concepts and mechanisms driving PCa progression through lncRNAs, providing a critical analysis of their impact on the disease's diverse characteristics. Besides, it discusses the potential of lncRNAs as diagnostics and therapeutic targets in PCa. Collectively, this work highlights state of art mechanistic comprehension and rigorous scientific approaches to advance our understanding of PCa and depict innovations in this evolving field of research.

A comprehensive review on the applications of ferrite nanoparticles in the diagnosis and treatment of breast cancer.

Various conventional treatments including endocrine therapy, radiotherapy, surgery, and chemotherapy have been used for several decades to treat breast cancer; however, these therapies exhibit various life-threatening and debilitating adverse effects in patients. Additionally, combination therapies are required for prompt action as well as to prevent drug resistance toward standard breast cancer medications. Ferrite nanoparticles (NPs) are increasingly gaining momentum for their application in the diagnosis and treatment of breast cancer. Spinel ferrites are particularly used against breast cancer and have shown in vitro and in vivo better efficacy as compared to conventional cancer therapies. Magnetic resonance imaging contrast agents, magnetic particle imaging tracers, cell separation, and immune assays are some aspects related to the diagnosis of breast cancer against which different ferrite NPs have been successfully evaluated. Moreover, citrate-coated nickel ferrite, Mg/Zn ferrites, poly amidoamine dendrimers, cobalt ferrites, graphene oxide cobalt ferrites, doxorubicin functionalized cobalt ferrites, chitosan-coated zinc ferrites, PEG-coated cobalt ferrite, and copper ferrite NPs have demonstrated antiproliferative action against different breast cancer cells. Oxaliplatin-loaded polydopamine/BSA-copper ferrites, functionalized cobalt and zinc ferrites of curcumin, oxaliplatin-copper ferrite NPs, tamoxifen/diosgenin encapsulated ZnO/Mn ferrites, and fabricated core-shell fibers of doxorubicin have been developed to increase the bioavailability and anti-proliferative effect and decrease the toxicity of anticancer drugs. These ferrite NPs showed an anticancer effect at different doses in the presence or absence of an external magnetic field. The present review covers the in-depth investigations of ferrite NPs for the diagnosis and management of breast cancer.

Prognostic value of whole-body dynamic 18F-FDG PET/CT Patlak in diffuse large B-cell lymphoma.

Objective: This study aims to investigate the significance of interim whole-body dynamic 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak parameters for predicting the prognosis of patients with diffuse large B-cell lymphoma. To estimate the predictive value of the whole-body dynamic 18F-FDG PET/CT Patlak parameter for 2-year progression-free survival (PFS) and 2-year overall survival (OS). Methods: This study reports the findings of 67 patients with diffuse large B-cell lymphoma (DLBCL). These patients underwent interim whole-body dynamic 18F-FDG PET/CT scans from June 2021 to January 2023 at the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University. The predictive values of maximum standard uptake value (SUVmax), maximum of net glucose uptake rate (Kimax) and the predictive model combining Kimax and interim treatment response on the prognosis of patients was analyzed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival curves and log-rank tests were used for survival analysis. Univariate and multivariate analyses were performed to screen for independent prognostic risk factors. Results: After a median follow-up of 18 months, 21 patients (31.3%) experienced disease recurrence or death. The cut-off values for the SUVmax and the Kimax were 6.1 and 0.13 µmol min-1·ml-1, respectively. Ann Arbor stage, IPI, SUVmax, Kimax and interim treatment response were associated with PFS and OS in the univariate analysis. However, only Kimax and interim treatment response were independent influences on PFS and OS in multivariate analysis. Conclusion: Interim whole-body dynamic 18F-FDG PET/CT Patlak imaging has significant prognostic value in patients with DLBCL. Among them, the interim dynamic parameter Kimax showed the best predictive value for prognosis compared with the interim SUVmax and interim treatment response. The predictive model established by Kimax and the interim treatment response allowed for the accurate stratification of the prognostic risk of DLBCL.

Correction: Khan et al. Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells. Int. J. Mol. Sci. 2022, 23, 10665.

In the original publication by Khan et al [...].

Stem cells-derived exosomes alleviate neurodegeneration and Alzheimer's pathogenesis by ameliorating neuroinflamation, and regulating the associated molecular pathways.

Amyloid beta (Aß) aggregation and tau hyper phosphorylation (p-tau) are key molecular factors in Alzheimer's disease (AD). The abnormal formation and accumulation of Aß and p-tau lead to the formation of amyloid plaques and neurofibrillary tangles (NFTs) which ultimately leads to neuroinflammation and neurodegeneration. ß- and γ-secretases produce Aß peptides via the amyloidogenic pathway, and several kinases are involved in tau phosphorylation. Exosomes, a recently developed method of intercellular communication, derived from neuronal stem cells (NSC-exos), are intriguing therapeutic options for AD. Exosomes have ability to cross the BBB hence highly recommended for brain related diseases and disorders. In the current study, we examined how NSC-exos could protect human neuroblastoma cells SH-SY5Y (ATCC CRL-2266). NSC-exos were derived from Human neural stem cells (ATCC-BYS012) by ultracentrifugation and the therapeutic effects of the NSC-exos were then investigated in vitro. NSC-exos controlled the associated molecular processes to drastically lower Aß and p-tau. A dose dependent reduction in ß- and γ-secretase, acetylcholinesterase, GSK3ß, CDK5, and activated α-secretase activities was also seen. We further showed that BACE1, PSEN1, CDK5, and GSK-3ß mRNA expression was suppressed and downregulated, while ADAM10 mRNA was increased. NSC- Exos downregulate NF-B/ERK/JNK-related signaling pathways in activated glial cells HMC3 (ATCC-CRL-3304) and reduce inflammatory mediators such iNOS, IL-1ß, TNF-α, and IL-6, which are associated with neuronal inflammation. The NSC-exos therapy ameliorated the neurodegeneration of human neuroblastoma cells SH-SY5Y by enhancing viability. Overall, these findings support that exosomes produced from stem cells can be a neuro-protective therapy to alleviate AD pathology.

The prevalence of prostate cancer in Pakistan: A systematic review and meta-analysis.

Background: Prostate cancer is a significant public health issue, ranking as the second most common cancer and the fifth leading cause of cancer-related deaths in men. In Pakistan, the prevalence of prostate cancer varies significantly across published articles. This study aimed to determine the pooled prevalence of prostate cancer and its associated risk factors in Pakistan. Methods: MEDLINE (via PubMed), Web of Science, Google Scholar, and local databases were searched from inception until March 2023, using key search terms related to the prevalence of prostate cancer. We considered a random-effects meta-analysis to derive the pooled prevalence and relative risks with 95% CIs. Two investigators independently screened articles and performed data extraction and risk of bias analysis. We also conducted meta-regression analysis and stratification to investigate heterogeneity. This study protocol was registered at PROSPERO, number CRD42022376061. Results: Our meta-analysis incorporated 11 articles with a total sample size of 184,384. The overall pooled prevalence of prostate cancer was 5.20% (95% CI: 3.72-6.90%), with substantial heterogeneity among estimates (I2 = 98.5%). The 95% prediction interval of prostate cancer was ranged from 1.74%-10.35%. Subgroup meta-analysis revealed that the highest pooled prevalence of prostate cancer was in Khyber Pakhtunkhwa (8.29%; 95% CI: 6.13-10.74%, n = 1), followed by Punjab (8.09%; 95% CI:7.36-8.86%, n = 3), while the lowest was found in Sindh (3.30%; 95% CI: 2.37-4.38%, n = 5). From 2000 to 2010 to 2011-2023, the prevalence of prostate cancer increased significantly from 3.88% (95% CI: 2.72-5.23%) to 5.80% (95% CI: 3.76-8.24%). Conclusions: Our meta-analysis provides essential insights into the prevalence of prostate cancer in Pakistan, highlighting the need for continued research and interventions to address this pressing health issue.

Adverse health effects and mechanisms of microplastics on female reproductive system: a descriptive review.

Microplastics (MPs), with a diameter of less than 5 mm, include polymers such as polystyrene, polypropylene, and polyethylene. The MPs occur in different morphologies including fragments, beads, fibers, and films that are swallowed by fresh water and land-based animals and enter their food chain, where they produce hazardous effects such as uterine toxicity, infertility, and neurotoxicity. The aim of this review is to explore the effects of polystyrene MPs (PS-MPs) on the female reproductive system and understand the mechanisms by which they produce reproductive toxicity. Several studies suggested that the exposure to PS-MPs increased the probability of larger ovaries with fewer follicles, decreased the number of embryos produced, and decreased the number of pregnancies in female mice. It also changed sex hormone levels and caused oxidative stress, which could have an impact on fertility and reproduction. Exposure to PS-MPs caused the death of granulosa cells through apoptosis and pyroptosis via activation of the NLRP3/caspase pathway and disruption of the Wnt-signaling pathway. Activation of TL4/NOX2 caused the uterine fibrosis resulting in endometrium thinning. The PS-MPs had a negative impact on ovarian capacity, oocyte maturation, and oocyte quality. Furthermore, the PS-MPs disrupted the hypothalamus-pituitary-gonadal axis in marine animals, resulting in a decrease in hatching rate and offspring body size, causing trans-generational effects. It also reduced fecundity and produced germ-line apoptosis. The main focus of this review was to explore the different mechanisms and pathways through which PS-MPs adversely impact the female reproductive system.

Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy.

In the last ten years, it has become increasingly clear that tumor-infiltrating myeloid cells drive not just carcinogenesis via cancer-related inflammatory processes, but also tumor development, invasion, and metastasis. Tumor-associated macrophages (TAMs) in particular are the most common kind of leucocyte in many malignancies and play a crucial role in establishing a favorable microenvironment for tumor cells. Tumor-associated macrophage (TAM) is vital as the primary immune cell subset in the tumor microenvironment (TME).In order to proliferate and spread to new locations, tumors need to be able to hide from the immune system by creating an immune-suppressive environment. Because of the existence of pro-tumoral TAMs, conventional therapies like chemotherapy and radiotherapy often fail to restrain cancer growth. These cells are also to blame for the failure of innovative immunotherapies premised on immune-checkpoint suppression. Understanding the series of metabolic changes and functional plasticity experienced by TAMs in the complex TME will help to use TAMs as a target for tumor immunotherapy and develop more effective tumor treatment strategies. This review summarizes the latest research on the TAMs functional status, metabolic changes and focuses on the targeted therapy in solid tumors.

Pterostilbene reduces the progression of atopic dermatitis via modulating inflammatory and oxidative stress biomarkers in mice.

Atopic dermatitis (AD) is one of the most prevalent chronic skin inflammatory disorders requiring continuous treatment and care. Pterostilbene (PTN) belongs to stilbene and is a polyphenolic compound of natural origin. It is similar to resveratrol and has analogous anti-inflammatory, anti-oxidant, and anti-carcinogenic characteristics. This study was intended to evaluate the effect of PTN against atopic dermatitis. The disease was induced by sensitization with 2,4-dinitrochlorobenzene (DNCB) in mice. The standard control group (SCG) received topical 0.1% tacrolimus (TC), whereas three other treatment groups received daily topical PTN at 0.2, 0.6, and 1% w/w for 28 days. Dermatitis scoring, ear thickness, and body weight of animals were weekly determined while other parameters were assessed at the termination of the experiment. PTN reduced the ear weight, skin thickness, and the weight and size of thymus glands and spleen in comparison with diseased animals. PTN also reduced the elevated immunoglobulin E (IgE) level and blood inflammatory cells in diseased mice. The histopathological findings showed a decreased epidermal thickness in PTN-treated groups. Moreover, treatment with PTN improved the amount of oxidative stress markers in the skin of the diseased mice. The expressions of IL-4, IL-6, TNF-α, and NF-κB in the skin of diseased mice were also reduced by PTN. This study concludes that PTN ameliorated the symptoms of atopic dermatitis through the reduction of inflammation, oxidative damage, and inflammatory cytokines in the skin of diseased animals. Therefore, PTN must be further investigated for the treatment of AD complications and other inflammatory skin disorders.

Role of ionizing radiation activated NRF2 in lung cancer radioresistance.

Radiotherapies are commonly used to target remaining tumor niches after surgery of solid tumors but are restricted due to therapeutic resistance. Several pathways of radioresistance have been reported in various cancers. This study investigates the pivotal role of Nuclear factor-erythroid 2-related factor 2 (NRF2) in the activation of DNA damage repair in lung cancer cells after x-rays exposure. To explore the NRF2 activation after ionizing irradiations, this study uses a knockdown of NRF2, which shows potential DNA damage after x-rays irradiation in lung cancers. This work further shows that NRF2 knockdown disrupts damaged DNA repair by inhibiting DNA-dependent protein kinase catalytic subunit. At the same time, NRF2 knockdown by shRNA considerably disparate homologous recombination by interfering with Rad51 expression. Further investigation of the associated pathway reveals that NRF2 activation mediates DNA damage response via the mitogen-activated protein kinase (MAPK) pathway as the knockout of NRF2 directly enhances intracellular MAPK phosphorylation. Similarly, both N-acetylcysteineand constitutive knockout of NRF2 disrupt DNA-dependent protein kinase catalytic subunit, while NRF2 knockout failed to upregulate Rad51 expression after irradiation in-vivo. Taken together, these findings advocate NRF2 plays a critical role in the development of radioresistance by upregulating DNA damage response via the MAPK pathway, which can be of great significance.

The mystery of post-cholecystectomy persistent bile leak: a case report.

Laparoscopic cholecystectomy (LC) is commonly performed for benign gallbladder diseases. Biliary leak is the most common complication of bile duct injury following this surgery. We report a case of persistent bile leak following the procedure despite endoscopic and radiological management. A female patient presented to the hepatopancreatobiliary unit of the Bahria International Hospital (Orchard), Lahore, with complaint of persistent bile leakage after laparoscopic cholecystectomy performed elsewhere. She had been investigated in various hospitals but the cause of the persistent bile leak remained a mystery and she was offered surgery. After real time fluoroscopic contrast enhanced imaging, further confirmed by a Computerised Tomography (CT) Scan of the abdomen, it was revealed that the persistent bile leak in the drain was due to iatrogenic injury of the duodenum secondary to percutaneous catheter insertion. The patient was managed non-surgically. She remained stable. This is a rare complication of one of the most common surgical procedures performed in the world.

Tumor micro-environment sensitive release of doxorubicin through chitosan based polymeric nanoparticles: An in-vitro study.

Conventional chemotherapy poses toxic effects to healthy tissues. A therapeutic system is thus required that can administer, distribute, metabolize, and excrete medicine from human body without damaging healthy cells. This is possible by designing a therapeutic system that can release drug at specific target tissue. In current work, novel chitosan (CS) based polymeric nanoparticles (PNPs) containing N-isopropyl acrylamide (NIPAAM) and 2-(di-isopropyl amino) ethyl methacrylate (DPA) are designed. The presence of available functional groups i.e. OH- (3262 cm-1), -NH2 (1542 cm-1), and CO (1642 cm-1), was confirmed by Fourier Transform Infra-red Spectrophotometry (FTIR). The surface morphology and average particle size (175 nm) was determined through Scanning Electron Microscope (SEM). X-Ray Diffractometry (XRD) studies confirmed the amorphous nature and excellent thermal stability of PNPs up to 100 °C with only 2.69% mass loss was confirmed by Thermogravimetric analysis (TGA). The pH sensitivity of such PNPs for release of encapsulated doxorubicin at malignant site was investigated. The encapsulation efficiency of PNPs was 89% (4.45 mg/5 mg) for doxorubicin (a chemotherapeutic) measured by using UV-Vis Spectrophotometer. The drug release profile of loaded PNPs was 88% (3.92 mg/4.45 mg) at pH 5.3, in 96 h. PNPs with varying DPA concentration can effectively be used to deliver chemotherapeutic agents with high efficacy.

Alternative treatment of polycystic ovary syndrome: pre-clinical and clinical basis for using plant-based drugs.

The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an endocrine disorder that occurs in approximately one in seven women. Among these PCOS patients, two thirds will not ovulate on a regular basis and seek treatment for ovulation induction. The symptoms vary in their severity, namely ovulation disorders, excessive androgen levels, or polycystic ovarian morphology. All these symptoms require a therapeutic approach. Many drugs are used to eradicate PCOS symptoms, like metformin, clomiphene citrate, spironolactone, and pioglitazone. Long-term treatment is required to achieve the desired outcome, which is often accompanied by significant adverse reactions. Some herbs and phytochemicals are equally effective for treating PCOS and produce minimal side effects. Recently, herbal products are gaining popularity due to their wide biological activities, safety, availability, and efficacy. The present review covers aetiology, current treatment, pathophysiology, and detailed pre-clinical and clinical studies on plants and phytochemicals that are proven to be useful for the treatment of symptoms associated with PCOS.

Tailoring Vanadium-Based Magnetic Catalyst by In Situ Encapsulation of Tungsten Disulfide and Applications in Abatement of Multiple Pollutants.

A magnetic nanocomposite of tungsten and vanadium was employed as a catalyst for the mitigation of water contaminants, including a carcinogenic dye (Congo red, CR), a widely used pesticide (glyphosate), and the bacterial strain Escherichia coli. Additionally, it was subjected to several characterization techniques. X-ray diffraction spectroscopy examination validated the synthesized nanoparticles' crystalline nature, and scanning electron microscopy and energy-dispersive X-ray analysis were employed to examine the morphology and elemental composition of the catalyst. The use of thermogravimetric analysis enabled the elaboration of the thermal behavior of tungsten sulfide-vanadium decorated with Fe2O3 nanoparticles. The experiments were conducted under visible light conditions. The highest levels of photodegradation of 96.24 ± 2.5% for CR and 98 ± 1.8% for glyphosate were observed following a 180 min exposure to visible light at pH values of 6 and 8, respectively. The quantum yields for CR and Gly were calculated to be 9.2 × 10-3 and 4.9 × 10-4 molecules photon-1, respectively. The findings from the scavenger analysis suggest the involvement of hydroxyl radicals in the degradation mechanism. The study evaluated the inhibition of E. coli growth when exposed to a concentration of 0.1 g/10 mL of the photocatalyst, utilizing a 1 mL sample of the bacterial strain. The successful elimination of CR and glyphosate from water-based solutions, along with the subsequent antibacterial experiments, has substantiated the efficacy of the photocatalyst in the field of environmental remediation.

A novel technique for prevention of anterior fistula and facilitation of alveolar cleft repair: Gingivoperiosteoplasty with palatoplasty.

Background & Objectives: The Cleft palate is one of the most commonly encountered congenital deformity in plastic surgery clinics and can be associated with cleft lip and alveolus. Though palate repair can be associated with several complications, the most frequent and troublesome is anterior fistula formation. Various technical modifications are in practice to avoid this dreaded complication. We have started combining gingivoperiosteoplasty with palate repair to avoid postoperative anterior fistula formation and to close alveolar cleft at the same time. Methods: A prospective study was performed at the department of plastic and reconstructive surgery, Liaquat National Hospital, Karachi and selected patients were enrolled in the study after informed consent. A total of 15 patients were operated on from January 2017 to December 2020. All patients had cleft palate repair along with primary gingivoperiosteoplasty (GPP) at the age of standard palatal repair. Buccal/oral and nasal layers of the alveolus were dissected as per standard gingivoperiosteoplasty and repaired in continuation with nasal and oral layers of the palate. Postoperatively, the standard cleft palate repair protocol was followed. Follow-up was done at four weeks, 12 weeks, and six months and repair integrity was checked. Future follow-up at 4-5 years of age is planned to see the effect on alveolar collapse, bone growth, and the need for secondary bone grafting. Results: All patients were followed up regularly. None had a complication of fistula. The repairs of both palate and alveolus remained intact. Patients were kept on the follow-up to assess the need for alveolar bone grafting in the future. Conclusion: Gingivoperiosteoplasty combined with the palatal repair is a novel technique for the prevention of anterior palatal fistula.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells.

Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), vascular endothelial growth factor receptor-2 (VEGFR-2), and nuclear factor kappa B (NF-κB). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.

Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights.

Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.

Biodegradable Magnetic Molecularly Imprinted Anticancer Drug Carrier for the Targeted Delivery of Docetaxel.

Molecularly imprinted biodegradable polymers are receiving considerable attention in drug delivery due to their ability of targeted recognition and biocompatibility. This study reports the synthesis of a novel fluorescence-active magnetic molecularly imprinted drug carrier (MIDC) using a glucose-based biodegradable cross-linking agent for the delivery of anticancer drug docetaxel. The magnetic molecularly imprinted polymer (MMIP) was characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy, and vibrating sample magnetometry (VSM). The MMIP presented a magnetization value of 0.0059 emu g-1 and binding capacity of 72 mg g-1 with docetaxel. In vitro and in vivo studies were performed to observe the effectiveness of the MIDC for drug delivery. The cell viability assay suggested that the MMIP did not present toxic effects on healthy cells. The magnetic property of the MMIP allowed quick identification of the drug carrier at the target site by applying the external magnetic field to mice (after 20 min of loading) and taking X-ray images. The novel MMIP-based drug carrier could thus deliver the drug at the target site without affecting the healthy cells.