New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.

Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system's power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract.

Disseminated mycobacterium genavense infection with central nervous system involvement in an HIV patient: a case report and literature review.

BACKGROUND: Immunodeficient patients, particularly HIV patients, are at risk of opportunistic infections. Nontuberculous mycobacteria can cause severe complications in immunodeficient patients. CASE PRESENTATION: We describe a 57-year-old HIV patient, primarily presented with coughs and constitutional symptoms, with a unique Mycobacterium genavense abdominal, pulmonary, and central nervous system infection, accompanied by intracranial masses. CONCLUSION: The diagnosis of NTM, including M. genavense, must always be considered by clinicians in immunodeficient patients, especially those with HIV, who have a compromised immune system.

Predictors of major adverse cardiac and cerebrovascular events after percutaneous coronary intervention in older adults: a systematic review and meta-analysis.

AIM: We systematically reviewed and meta-analyzed the predictors of major adverse cardiac and cerebrovascular events (MACE/MACCE) in older adults who underwent PCI. METHODS: Three databases, PubMed, Embase, and Scopus, were searched for observational studies considering the out-of-hospital MACE/MACCE in adults ≥ 60 years old with coronary artery disease (acute or chronic) who underwent PCI. Studies were eligible if they had determined at least two statistically significant predictors of MACE/MACCE by multivariable analysis. We used the QUIPS tool to evaluate the risk of bias in the studies. Random-effects meta-analysis was utilized to pool the hazard ratios (HRs) of the most reported predictors. RESULTS: A total of 34 studies were included in the review. Older age (HR = 1.04, 95% Confidence Interval (CI): 1.03-1.06, P-value < 0.001), diabetes (HR = 1.36, 95% CI: 1.22-1.53, P < 0.001), history of myocardial infarction (MI) (HR = 1.88, 95% CI: 1.37-2.57, P < 0.001), ST-elevation MI (STEMI) at presentation (HR = 1.72, 95% CI: 1.37-2.18, P < 0.001), reduced left ventricular ejection fraction (LVEF) (HR = 2.01, 95% CI: 1.52-2.65, P < 0.001), successful PCI (HR = 0.35, 95% CI: 0.27-0.47, P < 0.001), eGFR (HR = 0.99, 95% CI: 0.97-1.00; P-value = 0.04) and left main coronary artery (LMCA) disease (HR = 2.07, 95% CI: 1.52-2.84, P < 0.001) were identified as predictors of MACE. CONCLUSION: We identified older age, diabetes, history of MI, STEMI presentation, lower LVEF, and LMCA disease increased the risk of MACE/MACCE after PCI in older adults. Meanwhile, higher eGFR and successful PCI predicted lower adverse events risk. Future studies should focus on a more robust methodology and a precise definition of MACE. REGISTRATION: PROSPERO (CRD42023480332).

Recent advances in mesenchymal stem/stromal cells (MSCs)-based approaches for osteoarthritis (OA) therapy.

Recently, mesenchymal stem/stromal cells (MSCs) transplantation has been introduced as a promising option to support cartilage structure and improve its function in preclinical models and patients suffering from osteoarthritis (OA). MSCs strongly provoke their preferred influence in vivo by inhibiting the inflammatory responses and applying immunomodulation by releasing anti-inflammatory mediators such as transforming growth factor-ß and interleukin-10. Such mediators downregulate fibroblast-like synoviocytes growth and migration, leading to chondroprotection. Furthermore, improving the chondrocyte proliferation and extracellular matrix hemostasis in addition to the suppression of the matrix metalloproteinases activities can support cartilage tissue organization. In this light, various published results have demonstrated that MSCs therapy can considerably decrease pain and restore knee function in OA patients. In the current review, we have concentrated on recent advances in MSCs-based therapeutics to elicit both chondrogenic and chondroprotective impacts in OA patients, focusing on the last decade in vivo results.

Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis.

BACKGROUND: The tumor necrosis factor (TNF)-related apoptosis-inducing ligand, TRAIL, an apoptosis-inducing cytokine, has attracted much attention in the treatment of cancer for its selective toxicity to malignant rather than normal cells. However, the apoptosis-inducing ability of TRAIL is weaker than expected primarily due to cancer cell resistance. As one of the dietary flavonoids, kaempferol, has been shown to be antiproliferative and might have a protective effect against TRAIL resistance, particularly for hematologic malignancies. METHODS AND RESULTS: Here, we studied the potential of kaempferol to enhance the TRAIL-induced cytotoxicity and apoptosis in human chronic myelogenous leukemia (CML) cell line K-562, as well as the expression of specific genes with impact on TRAIL signal regulation. Analysis of flowcytometry data showed that treatment with kaempferol did enhance sensitivity of CML cells to pro-apoptotic effects of anti-TRAIL antibody. Although the gene expression levels were heterogeneous, cFLIP, cIAP1 and cIAP2 expression were generally downregulated where co-treatment of kaempferol and TRAIL was employed and these effects appeared to be dose-dependent. We further demonstrated that the expression of death receptors 4 and 5 tended to increase subsequent to the combination treatment. CONCLUSIONS: Consequently, it is reasonable to conclude that sensitization of chronic leukemia cells to TRAIL by kaempferol in vitro should be considered as a way of focusing clinical attention on leukemia therapy.

Under hypoxic conditions, MSCs affect the expression and methylation level of survival-related genes in ALL independent of apoptosis pathways in vitro.

Mesenchymal stem cells (MSCs) are one of the most prominent cells in the bone marrow. MSCs can affect acute lymphocytic leukemia (ALL) cells under hypoxic conditions. With this aim, we used MOLT-4 cells as simulators of ALL cells cocultured with bone marrow mesenchymal stem cells (BMMSCs) under hypoxic conditions in vitro. Then, mRNA and protein expression of the MAT2A, PDK1, and HK2 genes were evaluated by real-time PCR and Western blot which was also followed by apoptosis measurement by a flow-cytometric method. Next, the methylation status of the target genes was investigated by MS-qPCR. Additionally, candidate gene expressions were examined after treatment with rapamycin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We found that the mRNA expression of the candidate genes was augmented under the hypoxic condition in which MAT2A was upregulated in cocultured cells compared to MOLT-4, while HK2 and PDK1 were downregulated. Moreover, we found an association between gene expression and promoter methylation levels of target genes. Besides, expressions of the candidate genes were decreased, while their methylation levels were promoted following treatment with rapamycin. Our results suggest an important role for the BMMSC in regulating the methylation of genes involved in cell survival in hypoxia conditions; however, we found no evidence to prove the MSCs' effect on directing malignant lymphoblastic cells to apoptosis.

CAR-NK cell in cancer immunotherapy; A promising frontier.

Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR-natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti-cancer functions. Importantly, CAR-NK cells can be utilized as universal cell-based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor-associated antigens (TAAs). Indeed, CAR-NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR-NK cell anti-cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the "off-the-shelf" anti-cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR-NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

Induced pluripotent stem cells (iPSCs) as game-changing tools in the treatment of neurodegenerative disease: Mirage or reality?

Based on investigations, there exist tight correlations between neurodegenerative diseases' incidence and progression and aberrant protein aggregreferates in nervous tissue. However, the pathology of these diseases is not well known, leading to an inability to find an appropriate therapeutic approach to delay occurrence or slow many neurodegenerative diseases' development. The accessibility of induced pluripotent stem cells (iPSCs) in mimicking the phenotypes of various late-onset neurodegenerative diseases presents a novel strategy for in vitro disease modeling. The iPSCs provide a valuable and well-identified resource to clarify neurodegenerative disease mechanisms, as well as prepare a promising human stem cell platform for drug screening. Undoubtedly, neurodegenerative disease modeling using iPSCs has established innovative opportunities for both mechanistic types of research and recognition of novel disease treatments. Most important, the iPSCs have been considered as a novel autologous cell origin for cell-based therapy of neurodegenerative diseases following differentiation to varied types of neural lineage cells (e.g. GABAergic neurons, dopamine neurons, cortical neurons, and motor neurons). In this review, we summarize iPSC-based disease modeling in neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease. Moreover, we discuss the efficacy of cell-replacement therapies for neurodegenerative disease.

Mesenchymal stromal cells; a new horizon in regenerative medicine.

In recent decades, mesenchymal stromal cells (MSCs) biomedical utilizing has attracted worldwide growing attention. After the first report of the human MSCs obtaining from the bone marrow (BM) tissue, these cells were isolated from wide types of the other tissues, ranging from adipose tissue to dental pulp. Their specific characteristics, comprising self-renewality, multipotency, and availability accompanied by their immunomodulatory properties and little ethical concern denote their importance in the context of regenerative medicine. Considering preclinical studies, MSCs can modify immune reactions during tissue repair and restoration, providing suitable milieu for tissue recovery; on the other hand, they can be differentiated into comprehensive types of the body cells, such as osteoblast, chondrocyte, hepatocyte, cardiomyocyte, fibroblast, and neural cells. Though a large number of studies have investigated MSCs capacities in regenerative medicine in varied animal models, the oncogenic capability of unregulated MSCs differentiation must be more assessed to enable their application in the clinic. In the current review, we provide a brief overview of MSCs sources, isolation, and expansion as well as immunomodulatory activities. More important, we try to collect and discuss recent preclinical and clinical research and evaluate current challenges in the context of the MSC-based cell therapy for regenerative medicine.

Health insurance benefit package in Iran: a qualitative policy process analysis.

BACKGROUND: Insufficient transparency in prioritization of health services, multiple health insurance organizations with various and not-aligned policies, plus limited resources to provide comprehensive health coverage are among the challenges to design appropriate Health Insurance Benefit Package (HIBP) in Iran. This study aims to analyze Policy Process of Health Insurance Benefit Package in Iran. METHOD: Data were collected through semi-structured interviews with 25 experts, plus document analysis and observation, from February 2014 until October 2016. Using both deductive and inductive approaches, two independent researchers conducted data content analysis. We used MAXQDA.11 software for data management. RESULTS: We identified 10 main themes, plus 81 sub-themes related to development and implementation of HIBP. These included: lack of transparent criteria for inclusion of services within HIBP, inadequate use of scientific evidence to determine the HIBP, lack of evaluation systems, and weak decision-making process. We propose 11 solutions and 25 policy options to improve the situation. CONCLUSION: The design and implementation of HIBP did not follow an evidence-based and logical algorithm in Iran. Rather, political and financial influences at the macro level determined the decisions. This is rooted in social, cultural, and economic norms in the country, whereby political and economic factors had the greatest impact on the implementation of HIBP. To define a cost-effective HIBP in Iran, it is pivotal to develop transparent and evidence-based guidelines about the processes and the stewardship of HIBP, which are in line with upstream policies and societal characteristics. In addition, the possible conflict of interests and its harms should be minimized in advance.

Epigenetic-based therapy for colorectal cancer: Prospect and involved mechanisms.

Epigenetic modifications are heritable variations in gene expression not encoded by the DNA sequence. According to reports, a large number of studies have been performed to characterize epigenetic modification during normal development and also in cancer. Epigenetics can be regarded more widely to contain all of the changes in expression of genes that make by adjusted interactions between the regulatory portions of DNA or messenger RNAs that lead to indirect variation in the DNA sequence. In the last decade, epigenetic modification importance in colorectal cancer (CRC) pathogenesis was demonstrated powerfully. Although developments in CRC therapy have been made in the last years, much work is required as it remains the second leading cause of cancer death. Nowadays, epigenetic programs and genetic change have pivotal roles in the CRC incidence as well as progression. While our knowledge about epigenetic mechanism in CRC is not comprehensive, selective histone modifications and resultant chromatin conformation together with DNA methylation most likely regulate CRC pathogenesis that involved genes expression. Undoubtedly, the advanced understanding of epigenetic-based gene expression regulation in the CRC is essential to make epigenetic drugs for CRC therapy. The major aim of this review is to deliver a summary of valuable results that represent evidence of principle for epigenetic-based therapeutic approaches employment in CRC with a focus on the advantages of epigenetic-based therapy in the inhibition of the CRC metastasis and proliferation.

Quercetin sensitizes human myeloid leukemia KG-1 cells against TRAIL-induced apoptosis.

INTRODUCTION: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Conventional treatments are associated with cytotoxicity and systemic side effects. Hence, efforts in the field of cancer treatment are focused on finding the strategies which can specifically target the tumor cells without affecting the normal cells. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine which has the mentioned specificity, but the resistance of some cancer cells limits its use as a therapeutic strategy. Recent studies have shown that quercetin (QUR) can be used as a sensitizing agent alongside with TRAIL. The present study showed that QUR can increase the effect of TRAIL-induced cytotoxicity in KG-1 cells. MATERIALS AND METHODS: In this descriptive study, the IC50 dose for QUR in the KG-1 cell line was first determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Then, the cells were treated with TRAIL and QUR for 12, 24, and 48 hr. The rate of apoptosis was measured by Annexin V/propidium iodide assay. Also, the molecular evaluation of candidate genes was accomplished before and after the treatment. RESULTS: The results indicated that QUR could sensitize the KG-1 cells against the TRAIL-induced apoptosis. This outcome is achieved by increasing the messenger RNA expression levels of the death receptor genes and reducing the expression of antiapoptotic proteins, as well as decreasing the expression of the NF-κB subunit. CONCLUSION: Our findings suggest that QUR can sensitize the acute myeloid KG-1 cells against TRAIL. Moreover, the combinational therapy of these agents might promisingly improve the clinical efficacy of TRAIL in patients with AML.

Epigenetic mechanisms are behind the regulation of the key genes associated with the osteoblastic differentiation of the mesenchymal stem cells: The role of zoledronic acid on tuning the epigenetic changes.

Mesenchymal stem cells (MSCs) are multipotent stem cells and show distinct features such as capability for self-renewal and differentiation into several lineages of cells including osteoblasts, chondrocytes, and adipocytes. In this study, the methylation status of the promoter region of zinc finger and BTB domain containing 16 (ZBTB16), twist-related protein 1(Twist1), de novo DNA methyltransferases 3A (DNMT3A), SRY-box 9 (Sox9), osteocalcin (OCN), and peroxisome proliferator-activated receptor γ2 (PPARγ2) genes and their messenger RNA (mRNA) expression levels were evaluated during the osteoblastic differentiation of MSCs (ODMSCs). We planned two experimental groups including zoledronic acid (ZA)-treated and nontreated cells (negative control) which both were differentiated into the osteoblasts. Methylation level of DNA in the promoter regions was assayed by methylation-specific-quantitative polymerase chain reaction (MS-qPCR), and mRNA levels of the target inhibitory/stimulatory genes during osteoblastic differentiation of MSCs were measured using real-time PCR. During the experimental induction of ODMSCs, the mRNA expression of the OCN gene was upregulated and methylation level of its promoter region was decreased. Moreover, Sox9 and PPARγ2 mRNA levels were attenuated and their promoter regions methylation levels were significantly augmented. However, the mRNA expression of the DNMT3A was not affected during the ODMSCs though its methylation rate was increased. In addition, ZA could enhance the expression of the ZBTB16 and decrease its promoter regions methylation and on the opposite side, it diminished mRNA expression of Sox9, Twist1, and PPARγ2 genes and increased their methylation rates. Intriguingly, ZA did not show a significant impact on gene expression and methylation levels the OCN and DNMT3A. We found that methylation of the promoter regions of Sox9, OCN, and PPARγ2 genes might be one of the main mechanisms adjusting the genes expression during the ODMSCs. Furthermore, we noticed that ZA can accelerate the MSCs differentiation to the osteoblast cells via two regulatory processes; suppression of osteoblastic differentiation inhibitor genes including Sox9, Twist1, and PPARγ2, and through promotion of the ZBTB16 expression.

Leukemia therapy by flavonoids: Future and involved mechanisms.

Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP-ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin-dependent kinases. Furthermore, attenuation of neclear factor-κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

Down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (death receptor 5, DR5), TRAIL-R3 (decoy receptor 1, DcR1), TRAIL-R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis-inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely. According to diverse ranges of examinations, intracellular anti-apoptotic proteins, such as cellular-FLICE inhibitory protein (c-FLIP), apoptosis inhibitors (IAPs), myeloid cell leukemia sequence 1 (MCL-1), BCL-2, BCL-XL, and survivin play key role in cancer cells resistance to TRAIL. These proteins attenuate cancer cells sensitivity to TRAIL via various functions, importantly through caspase cascade suppression. The c-FLIP avoids from caspase 8 activation by FADD via binding to caspase 8 cleavage of FADD. Moreover, it activates signaling pathways that involved in cancer cells survival and proliferation. Intriguingly, it appears that the down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP is effectiveness goal for TRAIL-resistant cancers therapy, because their up-regulation in association with poor prognosis has been observed in various types of TRAIL-resistant cancers. In this review, we tried to collect and examine investigations that researchers have been able to sensitize cancer cells to TRAIL through targeting of c-FLIP alone or with other intracellular anti-apoptotic proteins directly or indirectly. It seems that co-treatment of resistant cells by TRAIL with other therapeutic agents with the aim of intracellular anti-apoptotic proteins inhibition is hopeful and attractive approach to overcome various TRAIL-resistant cancers.

The rapid synthesis of 1,10-phenanthroline-5,6-diimine (Phendiimine) and its fascinating photo-stimulated behavior.

Here, for the first time, we report synthesis of 1,10-phenanthroline-5,6-diimine (Phendiimine) based on an acid catalysed SN2 reaction of 1,10-phenanthroline-5,6-dione and 2-picolylamine in EtOH as a solvent. The synthesized Phendiimine molecule showed excellent photo-sensitivity against visible light, together with photoluminescence in both water and ethanol and also, it showed electrochemical activity with Fe electrode in ethanol and H2SO4 solution. Tauc plot also showed Phendiimine is a direct band-gap semiconductor. The hot-point probe test also showed that it is a n-type semiconductor. The UV-vis. absorption maximum shift in two solvents (water and ethanol) demonstrates the solvatochromism behavior of the molecule. The practical significance of this work and its guiding implication for future related research can be outlined as follows. Based on the results obtained, it appears that the Phendiimine molecule could revolutionize the medical field, potentially in the design of artificial eyes, increasing the yield of photovoltaic cells through enhanced heat transfer, improving computers and industrial photo-cooling systems, serving as photo-controller in place of piezoelectric devices, functioning as electronic opt couplers, controlling remote lasers, changing convection in photothermal heaters, designing miniaturized real photo-stimulated motors, creating photo or thermal switches through spin crossover complexes, developing electronic light-dependent resistance (LDR) devices, constructing X-ray and gamma-ray detectors, designing intelligent clothing, creating photo dynamic tumour therapy (PDT) complexes, singlet fission materials in solar cells and more.

Magnetic cobalt metal organic framework for photocatalytic water splitting hydrogen evolution.

Using water as a renewable and safe energy source for hydrogen generation has reduced the need to use toxic fossil fuels. Photocatalytic approaches provide a worthy solution to avoid the high expenditure on complicated electrochemical pathways to promote Hydrogen Evolution Reactions. However, several types of photocatalysts including noble metal-based catalysts have already been in use for this purpose, which are generally considered high-cost as well. The present study aims to use the benefits of metal-organic frameworks (MOFs) with semiconductor-like characteristics, highly porous structures and high design flexibility. These properties of MOFs allow more efficient and effective mass transport as well as exposure to light.in this paper, using MOF technology and benefiting from the characteristics of Fe3O4 nanoparticles as catalyst support for more efficient separation of catalyst, we have synthesized a novel composite. Our proposed photocatalyst demonstrates efficient harvest of light in all wavelengths from UV to visible to generate electron/hole pairs suitable for water splitting with a turnover frequency of 0.222 h-1 at ambient conditions without requiring any additives.

Conversion of a Failed Hip Hemiarthroplasty to Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

Background: Hip hemiarthroplasty (HA) and total hip arthroplasty (THA) are common treatments for femoral neck fractures in elderly patients. Despite HA's advantages of shorter operative times, less blood loss, and lower initial costs compared to primary THA, it may lead to conversion THA (cTHA). Our objectives are to evaluate the impact of conversion from HA to THA on Harris hip scores (HHS), compare complication rates between cTHA, revision THA, and primary THA, and assess the rates and types of complications following cTHA. Methods: A systematic review and meta-analysis were performed, evaluating studies published until 2023, with inclusion criteria entailing studies that explored outcomes and complications following cTHA of failed HA. Data extraction focused on variables such as postoperative HHS and complication rates, including periprosthetic joint infection, periprosthetic fracture, dislocation, stem loosening, acetabular loosening, and overall revision. Results: This study included 28 retrospective studies (4699 hips), showing a mean increase in HHS by 39.1 points, indicating a significant improvement from preoperative levels. Complication rates were detailed, with a 6.4% rate of periprosthetic joint infection, 2.2% for periprosthetic fracture, 7.6% dislocation, 1.6% stem loosening, 1.9% acetabular loosening, and an overall re-revision rate of 8.7%. Conclusions: Conversion from HA to THA generally results in improved functional outcomes, as evidenced by HHS improvements. Despite the positive impact on HHS, cTHAs are associated with notable risks of complications and the need for further revision surgeries. Level of Evidence: IV.

Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside.

A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors.