BACKGROUND: The developmental biology for the nonalcoholic fatty liver disease and coronary heart disease are known but elaborative ideas of triglycerides phenomenon in the embryo-genesis of the liver and the heart are still not clear. OBJECTIVE: The aim of the study was to relate different triglycerides like LXRα, LPL, LDL R, PPARG-, and SREBP-1C expression in the high fat-fed mice with the normal-fed diet mice in the process of developmen-tal and embryo-genesis biology. METHODS: Tissue preparation was done by RIPA lysis. Different protein content was obtained via western blot for the 6 samples namely A.3 months embryo B.4 months embryo C.Birth day embryo D.3 days infant E. 2 weeks infant F. 4 weeks infant. Protein lysates from the heart tissues of the mice were obtained via ho-mogenization and centrifugation. Hematoxylin and Eosin staining (H and E) were done to see the fat droplets in the liver tissues at the different developmental stages. RESULT: LXRα,SREBP-1C expression in 3 months embryo and 4 months embryo is highly expressed in the high-fat diet. LDL-R in the high-fat diet mice is increased in 3 days infant heart but in 3 months and 4 months embryo it has low expression but from the 0th day to the 4 weeks the expression is in a decreasing trend. Similarly, LPL is highly expressed in 3 months embryo and 0th day(Birthday) and thus low expression indecreasing order until 4 weeks infant. Thus, these results collectively show that a maternal HF diet in-creases the expression of proteins such as LPL, and LDLr in the embryo phase and thus getting normal ex-pressions in the adult phase that facilitate Triglycerides (TAG) hydrolysis across the liver and the heart. Also, maternal high-fat diet increases the SREBP1c expression, leading to stimulation of LPL Expression. CONCLUSION: In summary, using a pregnant mice model, we found that a maternal high-fat diet increases fe-tal fat accumulation. Elevated placental LPL activity and expression of genes that facilitate placental lipid transport suggest that enhanced placental lipid transport may play a key role in maternal nutrition and obesi-ty-induced fetal fat accumulation.

Oral cancers are prevalent in the human population, particularly in unindustrialized countries. In 90 % of oral cancers, the tumors arise from squamous cells, which is called oral squamous cell carcinoma (OSCC). Despite new treatment strategies, the morbidity and mortality rates are still high. Current treatment options including surgery, chemotherapy, and radiotherapy are not effective in the treatment of the tumor. Cell therapy with mesenchymal stem cells (MSCs) is considered one of the leading strategies in cancer treatment. However, the field of MSC therapy in OSCC is immature and ongoing studies are being conducted in experimental and pre-clinical studies. Here, we reviewed these studies to figure out whether the use of MSCs could be worthwhile in OSCC therapy or not. Both native and engineered MSCs as well as their secretome have been used in the treatment of OSCC. It seems that genetically modified MSCs or their secretome could inhibit the tumorigenesis of OSCC. However, further pre-clinical studies are required to come to a conclusion.

BACKGROUND AND OBJECTIVE: The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) was originally identified in the Pacific oyster Crassostrea Gigas. DHMBA has been shown to prevent oxidative stress by scavenging radicals and enhance the production of antioxidant proteins. However, the pharmacologic role of DHMBA has been poorly understood. Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines are produced in macrophages with stimulation of lipopolysaccharide (LPS) and are used as biomarkers that cause diverse disease conditions. Therefore, this study has been undertaken to elucidate whether DHMBA expresses anti-inflammatory effects in in vitro mouse macrophage RAW264.7 cells. METHODS: Mouse macrophage RAW264.7 cells were cultured in a medium containing 10% fetal bovine serum (FBS) with or without DHMBA (1-1000 µM). RESULTS: Culturing with DHMBA (1-1000 µM) suppressed the growth and stimulated the death of RAW264.7 cells in vitro, leading to a decrease in cell number. Treatment with DHMBA reduced the levels of Ras, PI3K, Akt, MAPK, phospho-MAPK, and mTOR, which are signalling factors to promote cell proliferation, and it raised the levels of p53, p21, Rb, and regucalcin, which are cell growth suppressors. DHMBA treatment elevated caspase-3 and cleaved caspase-3 levels. Interestingly, DHMBA treatment repressed the production of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1β, or prostaglandin E2, which were enhanced by LPS stimulation. Notably, the levels of NF-κB p65 increased by LPS treatment, and this augmentation was repressed by DHMBA treatment. Moreover, LPS treatment stimulated osteoclastogenesis of RAW264.7 cells. This stimulation was blocked by DHMBA treatment, and this effect was not caused by the presence of an NF-κB signalling inhibitor. CONCLUSION: DHMBA was found to potentially suppress the activity of inflammatory macrophages in vitro, suggesting its therapeutic usefulness in inflammatory conditions.

BACKGROUND: The role of deficiency of vitamin D in a wide range of human cancer, including breast cancer, has been proven, but its role in benign breast diseases remains unknown. This study aimed to determine the prevalence of vitamin D deficiency in patients with fibrocystic breast (FB) disease. METHODS: First, the hospital prevalence of fibrocystic breast was determined by a cross-sectional study. Then, patients were divided into two groups by a case-control study; women with confirmed fibrocystic breasts based on breast pain, physical examination, and ultrasonography were included as a case group (N=48) and age-matched women without fibrocystic breasts were also included as a control group (N=48). After recording the demographic and gynecological characteristics and exposure to the sun, gynecological records, and family history of fibrocystic breast, the blood sample was taken to determine vitamin D. Data were analyzed by Stata software. RESULTS: The result indicated that the studied groups had significant differences in regards to weight, breast pain, the severity of breast pain, breast heaviness, family history of fibrocystic breast, history of breast disease, caffeine consumption, and exposure to sunlight (p <0.05), but did not show significant differences based on age, occupation, education, gynecological history, diabetes mellitus, hypertension, obesity and hypothyroidism, vegetable, fast food, and dairy products consumption. The frequency of vitamin D deficiency in the case group was 45.8%, and in the control group, it was 20.8%, and there was a statistically significant difference (p <0.05). CONCLUSION: Vitamin D deficiency is more common in women with fibrocystic breast disease and may play a role in the development of the disease.

Metabolic reprogramming in cancer cells is a strategy to meet high proliferation rates, invasion, and metastasis. Also, several researchers indicated that the cellular metabolism changed during the resistance to chemotherapy. Since glycolytic enzymes play a prominent role in these alterations, the ability to reduce resistance to chemotherapy drugs is promising for cancer patients. Oscillating gene expression of these enzymes was involved in the proliferation, invasion, and metastasis of cancer cells. This review discussed the roles of some glycolytic enzymes associated with cancer progression and resistance to chemotherapy in the various cancer types.

BACKGROUND: For any drug molecule, it is mandatory to pass the drug approval process of the concerned regulatory authority, before being marketed. The Food and Drug Administration (FDA), throughout the year, approves several new drugs for safety and efficacy. In addition to new drug approvals, FDA also works on improving access to generic drugs, aimed to lower the cost of drugs for patients and improve access to treatments. In the year 2022 twelve new drug therapies were approved for managing varying cancers. METHOD: This manuscript is focused to describe the pharmacological aspects including therapeutic uses, mechanisms of actions, pharmacokinetics, adverse effects, doses, indication for special cases, contraindications, etc., of novel FDA-approved anticancer drug therapies in the year 2022. RESULT: FDA has approved about 29% (11 out of 37) novel drug therapies for varying types of cancers such as lung cancer, breast cancer, prostate cancer, melanoma, leukemia, etc. The Center for Drug Evaluation and Research CDER has reported that 90% of these anticancer drugs (e.g. Adagrasib, Futibatinib, Mirvetuximabsoravtansine-gynx, Mosunetuzumab-axb, Nivolumab and relatlimab-rmbw, Olutasidenib, Pacritinib, Tebentafusp-tebn, Teclistamab-cqyv, and Tremelimumab-actl) as orphan drugs and recommended to treat rare or uncommon cancers such as non-small cell lung cancer, metastatic intrahepatic cholangio-carcinoma, epithelial ovarian cancer, follicular lymphoma, metastatic melanoma, metastatic uveal melanoma, etc. CDER has identified six anticancer drugs (e.g. Lutetium (177Lu)vipivotidetetraxetan, Mirvetuximabsoravtansine-gynx, Mosunetuzumab-axb, Nivolumab and relatlimab-rmbw, Tebentafusp-tebn, Teclistamab-cqyv) as first-in-class drugs i.e. drugs having different mechanisms of action from the already existing ones. The newly approved anticancer drugs shall provide more efficient treatment options for cancer patients. Three FDA-approved anticancer drugs in the year 2023 are also briefly described in the manuscript. CONCLUSION: This manuscript, describing the pharmacological aspects of eleven anticancer novel drug therapies approved by the FDA, shall serve as a helpful document for cancer patients, concerned academicians, researchers, and clinicians, especially oncologists.

Glaucoma is a group of diverse diseases characterized by cupping of the optic nerve head due to the loss of retinal ganglion cells. It is the most common cause of irreversible blindness throughout the word; therefore, its timely diagnosis and early detection through an ophthalmological examination are very important. We, herein, present the information on the epidemiology, pathophysiology, clinical diagnosis, and treatment of glaucoma. We also emphasize the investigations of the last decades that have allowed identifying numerous genes and susceptible genetic factors. We have also described in detail the genes whose mutations cause or contribute to the development of the disease.

Resveratrol (Res), a polyphenol found in red wine, has been shown to decelerate aging, the progressive loss of physiological integrity and cellular senescence, characterized by the inability to progress through the cell cycle. No successful clinical trials have yet to be completed in humans on dose limitations. Yet, the potent anti-aging and anti-senescence efficacy of Res has been documented in several in vivo animal models. In this review, we highlight the molecular mechanisms of Res efficacy in anti-aging disorders, such as diabetes, neurodegenerative disorders, eye diseases, and cardiovascular diseases.

Extracorporeal membrane oxygenation (ECMO) is identified as a novel therapeutic strategy that offers short-term support to the metabolism of the heart and lungs in humans. Recently, the clinical centers, which provide ECMO has increased rapidly worldwide. The indications for the use of ECMO in daily clinical practice were broadened dynamically. However, even with the widespread adoption of ECMO, it still remains significant morbidity and mortality, and the underlying mechanisms are still not elucidated. Notably, one of the vital complications during ECMO was proposed as the inflammatory progression within the extracorporeal circulation. Via the development of inflammatory response, patients with ECMO may further suffer from systemic inflammatory response syndrome (SIRS), posing serious risks to human health. Recently, growing evidence confirmed that through exposure of blood into the ECMO circuit could lead to the stimulation of the immune system which also facilitated the inflammatory response and systemic impaired. In the current review, the pathological development of inflammatory progression in patients with ECMO is well-listed. Furthermore, the relationship between immune-related activation and the development of inflammation is also summarized, which may further help us to decide the therapeutic strategies in daily clinical practice.

BACKGROUND: To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD. OBJECTIVE: In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation. METHODS: We examined the expression of TLX1 in pan cancer and LUAD, the relationship between TLX1 expression and clinical features, immune infiltration, its diagnostic and prognostic value, as well as TLX1 related pathways. The analysis included various statistical methods, including the Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis. TLX1 expression in LUAD cell lines was validated using qRT-PCR. RESULT: In LUAD patients, high expression of TLX1 was associated with T stage (P<0.001). High TLX1 expression was associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.18-2.1; P=0.002). And TLX1 [removed]HR: 1.619; 95% CI: 1.012-2.590; P=0.044) was independently correlated with OS in LUAD patients. TLX1 expression was associated with the pathways, including Rho GTPase effectors, DNA repair, TCF dependent signaling in response to WNT, signaling by Nuclear Receptors, signaling by Notch, chromatin-modifying enzymes, ESR-mediated signaling, cellular senescence, and transcriptional regulation by Runx1. TLX1 expression was correlated with aDC, Tcm, and TReg cells. The expression of TLX1 was significantly increased in LUAD cells compared to BEAS-2B cells. CONCLUSION: An association between high TLX1 expression and poor survival and immune infiltration was found in LUAD patients. There may be a potential role for TLX1 in diagnosis, prognosis, and immunotherapy for LUAD.

INTRODUCTION: This study implies the enhancement of apatinib killing effect in 4T1 tumor cells through constructing drug-loaded nanoparticles apatinib/Ce6@ZIF-8@Membranes (aCZM) to enhance tumor therapeutic targeting and reduce toxic side following sonodynamic therapy (SDT). METHODS: apatinib/Ce6@ZIF-8 (aCZ) were synthesized by in situ encapsulation, and aCZM were constructed by encapsulating the nanoparticles with extracted breast cancer 4T1 cell membranes. aCZM were characterized and tested for the stability by electron microscopy, and the membrane proteins on the nanoparticles' surface were assessed using SDS-PAGE gel electrophoresis. The cell viability of 4T1 cells following treatment with aCZM was tested using cell counting kit-8 (CCK-8). The uptake of nanoparticles was detected by laser confocal microscopy and flow cytometry, and the SDT-mediated production of reactive oxygen species (ROS) was verified by singlet oxygen sensor green (SOSG), electron spin resonance (ESR), and DCFH-DA fluorescent probes. The CCK-8 assay and flow cytometry using Calcein/PI were used to assess the antitumoral effect of aCZM nanoparticles under SDT. The biosafety of aCZM was further verified in vitro and in vivo using the hemolysis assay, routine blood test and H&E staining of vital organs in Balb/c mice. RESULTS: aCZM with an average particle size of about 210.26 nm were successfully synthesized. The results of the SDS-PAGE gel electrophoresis experiment showed that aCZM have a band similar to that of pure cell membrane proteins. The CCK-8 assay demonstrated the absence of effects on cell viability at a low concentration range, and the relative cell survival rate reached more than 95%. Laser confocal microscopy and flow cytometry analysis showed that aCZM treated group has the strongest fluorescence and the highest cellular uptake of nanoparticles. SOSG, ESR, and DCFH-DA fluorescent probes all indicated that the aCZM + SDT treated group has the highest ROS production. The CCK-8 assay also showed that when the ultrasound intensity was fixed at 0.5 W/cm2, the relative cell survival rates in the medium concentration group (10 μg/ml) (5.54 ± 1.26%) and the high concentration group (20 μg/ml) (2.14 ± 1.63%) were significantly lower than those in the low concentration group (5 μg/ml) (53.40 ± 4.25%). Moreover, there was a concentration and intensity dependence associated with the cell-killing effect. The mortality rate of the aCZM in the ultrasound group (44.95±3.03%) was significantly higher than that of the non-ultrasound (17.00±2.26%) group and aCZ + SDT group (24.85 ± 3.08%) (P<0.0001). The live and dead cells' staining (Calcein/PI) also supported this result. Finally, in vitro hemolysis test at 4 and 24 hours showed that the hemolysis rate of the highest concentration group was less than 1%. The blood routine, biochemistry, and H&E staining results of major organs in Balb/c mice undergoing nano-treatments showed no obvious functional abnormalities and tissue damage in 30 days. CONCLUSION: In this study, a multifunctional bionic drug delivery nanoparticles (aCZM) system with good biosafety and compatibility in response to acoustic dynamics was successfully constructed and characterized. This system enhanced apatinib killing effect on tumor cells and reduced toxic side effects under SDT.

The ubiquitous pandemic that emerged due to COVID-19 affected the whole planet. People all over the globe became vulnerable to the unpredictable emergence of coronavirus. The sudden emergence of respiratory disease in coronavirus infected several patients. This affected human life drastically, from mild symptoms to severe illness, leading to mortality. COVID-19 is an exceptionally communicable disease caused by SARS-CoV-2. According to a genomic study, the viral spike RBD interactions with the host ACE2 protein from several coronavirus strains and the interaction between RBD and ACE2 highlighted the potential change in affinity from the virus causing the COVID-19 outbreak to a progenitor type of SARS-CoV-2. SARS-CoV-2, which could be the principal reservoir, is phylogenetically related to the SARS-like bat virus. Other research works reported that intermediary hosts for the transmission of viruses to humans could include cats, bats, snakes, pigs, ferrets, orangutans, and monkeys. Even with the arrival of vaccines and individuals getting vaccinated and treated with FDA-approved repurposed drugs like Remdesivir, the first and foremost steps aimed towards the possible control and minimization of community transmission of the virus include social distancing, self-realization, and self-health care. In this review paper, we discussed and summarized various approaches and methodologies adopted and proposed by researchers all over the globe to help with the management of this zoonotic outbreak by following repurposed approaches.