BIO Integration

According to the prevalent concept of enhanced permeability and retention (EPR) effect proposed by Matsumura and Maeda in 1986 [1], nanoparticles can passively accumulate at the tumor site via gaps between endothelial cells (interendothelial gaps) in tumor-associated blood vessels that have abnormal structural integrity with pores ranging in size from submicron to micron. According to the paper published very recently by Sindhwani et al. [2], however, this classic concept needs to be modified or replaced by a new concept on the entry of nanoparticles into solid tumors. In their paper, Sindhwani and his team focused on how nanoparticles – represented by gold nanoparticles – enter tumors, by carrying out detailed visualization and data quantification on specific areas such as blood vessel gaps in tumors, accumulation and localization of nanoparticles in tumors, and also the comparison of transendothelially transported rate of nanoparticles to the rate of diffusion across blood vessel gaps. They analyzed 313 blood vessels across several tumor models, such as U87-MG glioma, 4T1 breast cancer, MMTV-PyMT breast cancer, PDX breast cancer and so on, and found only 26 gaps, which implied that gaps occurred at a very low frequency in all the aforementioned tumor types, which is consistent with the knowledge that gaps are also rare in tumor vessels from cancer patients. Furthermore, they demonstrated that only seven out of 26 openings were intercellular gaps (26.9%), while the rest were transendothelial pores. Through this study, they claimed that the main mechanism of nanoparticle tumor entry is through transendothelial openings. In fact, in 1997, researchers at Harvard University had proposed that the endothelial cell gaps that were induced by vasoactive mediators were mostly transcellular pores [3]. Feng et al. defined a novel endothelial cell organelle in the endothelial cells of both humans and animals, termed the vesiculovacuolar organelle (VVO) [3]. It participates in the regulation of intracellular transportation pathways during the transendothelial transport of soluble macromolecules. In this regard, there is a structural basis for nanoparticles to enter tumors through transendothelial pathways. According to this article, the extravasation of nanoparticles shows no significant relevance with tight junctions, fenestra, vesicles or endothelial gaps in blood vessels, which infers that nanoparticles primarily enter tumors by active transportation. Based on the aforementioned fact, there are two possible ends when nanoparticles enter the circulation. The first one is that nanoparticles are also capable of entering other organs by crossing the endothelial cells. Feng and coworkers showed that colloidal carbon could traverse endothelial cells via the development of pores; this mechanism does not require communication with the intercellular gap junction, nor do they need to disrupt intercellular junctions by gap formation in these vessels [4]. If this hypothesis of “nanoparticles entering normal vessels” proved to be true, this may explain why the efficiency of nanoparticle delivery to tumors is mostly lower than 1% in clinical experiments [5]. Hida et al. reported that endothelial cells in tumors exhibit different characteristics from normal vascular endothelial cells in terms of cell proliferation, migration ability, gene expression and response to growth factors and drugs [6]. Akino et al. showed that in human clear cell renal cell carcinoma (CCRCC), 22–58% (median, 33%) of tumor-associated endothelial cells were aneuploid, while normal endothelial cells were diploid [7]. Furthermore, tumor 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yatsen University, Guangzhou 510120, China

Phei Er Saw

Sangyong Jon

Understanding of the Entry Mechanism of Nanoparticles into Tumors Determines the Future Direction of Nanomedicine Development

理解纳米颗粒进入肿瘤的机制决定了纳米医学发展的未来方向

Abstract The tumor microenvironment (TME) has a crucial role in tumor development, metastasis, and recurrence. The chaotic and complex physical structure of the TME not only limits drug delivery but also contributes to the development of resistance to immunotherapy. Breaking the physical barrier limitation of the TME could further optimize the existing tumor treatment protocols. Physical stimulation, such as ionizing radiation, light, electricity, magnetic field, and ultrasound, modulate the TME by altering tumor vasculature, remodeling the extracellular matrix, and activating immune responses to achieve the goal of adjuvant to other tumor therapeutic approaches. In addition to adjuvant chemotherapy and immunotherapy, these physical stimulations also enhance the efficacy of other physical treatments for cancer. In this review we discuss the structural characteristics of TME and focus on the modulation of TME by different physical stimulations. We also analyze the adjuvant effects of these stimulations on other tumor therapies.

Zhili Guo

Non-Invasive Physical Stimulation to Modulate the Tumor Microenvironment: Unveiling a New Frontier in Cancer Therapy

非侵入性物理刺激调控肿瘤微环境：揭示癌症治疗新前沿

Abstract Cancer is a significant disease that poses a major threat to human health. Image-guided cancer therapy refers to a series of medical procedures that use imaging technology to precisely locate and treat cancer. Combining the dual characteristics of medical images and functional nanomaterial (NM) drug carriers, various integrated diagnosis and treatment probes have been developed for in vivo dynamic monitoring and therapeutic effect evaluation of drugs based on medical imaging. Copper (Cu)-based NMs have emerged as valuable products of nanotechnology due to their unique physicochemical properties, which are influenced by factors, such as size, shape, and surface properties. In the field of imaging, Cu-based NMs offer a combination of desirable characteristics, including fluorescence emission, contrast enhancement, and radiolabeling stability. These properties form the foundation for a wide range of imaging modalities. In addition, Cu-based NMs can be used as a carrier for diagnostic or therapeutic drugs and the synergistic effect of multiple therapeutic modalities can be realized by doping multiple transition metals into the heterostructures. These properties have become an important basis for imaging-guided therapy with Cu-based NMs. In this review we introduce biocompatible Cu-based NMs for image-guided cancer therapy and provide an overview of the promising outcomes in biomedical research.

Haonan Xu

Mingjie Li

Hellíada Vasconcelos Chaves

Vicente de Paulo Teixeira Pinto

Gerardo Cristino Filho

Meng Du

Mirna Marques Bezerra

Copper-Based Nanomaterials for Image-Guided Cancer Therapy

铜基纳米材料用于影像引导的癌症治疗

Abstract Chronic respiratory diseases impose a substantial health burden globally with increasing prevalence and mortality rates, especially in affluent nations. Recent studies underscore the escalating contribution to premature morbidity and mortality, highlighting the critical need for effective interventions. Inflammatory lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and idiopathic pulmonary fibrosis (IPF), have significant roles in this burden that are characterized by heightened inflammation affecting the airways or lung parenchyma, leading to obstructive or restrictive lung diseases. These conditions often exhibit acute and chronic components, which complicate disease classification and management. Current treatments for lung illnesses predominantly rely on systemic drug delivery, which may result in poor efficacy and adverse effects on other organs. Inhalation lung delivery presents a promising alternative, offering advantages, such as targeted drug deposition, reduced systemic side effects, and rapid onset of action. Despite these benefits, inhalation drug delivery systems are still in the developmental stage, particularly for targeted local delivery. Dry powder inhalers (DPIs) have emerged as a popular choice due to ease of use, high-dose delivery capability, and breath-activated mechanisms. This review delves into the intriguing world of pulmonary drug delivery, with a spotlight on DPIs. From the fascinating design principles to the potential for precision medicine, DPIs offer a glimpse into the future of respiratory care. By unravelling the mysteries of DPI formulation and performance assessment, this review aimed to propel the field forward, ushering in a new era of personalized and efficacious inhalation therapies for inflammatory lung diseases and beyond. Furthermore, this article delved into the identification of prevalent technologies within the DPI domain while also probing the prospective avenues of emerging development. Such insights aim to assist researchers in making informed decisions regarding relevant research and development pursuits.

Amir R. Tamboli

Vishal D. Yadav

Sameer J. Nadaf

Vaishnavi V. Nivekar

Ketaki S. Salve

Ennus T. Tamboli

Akshay M. Nalawade

Exploring the Frontier of Inhalation Therapy: A Review of Dry Powder Inhalers for Precision Management of Inflammatory Lung Diseases

探索吸入疗法的前沿：干粉吸入器在炎症性肺疾病精准管理中的回顾

Abstract Background: Diabetes mellitus remains a global health concern, because of its associated complications, including diabetic nephropathy. Glimepiride, a sulfonylurea derivative, and rutin, a flavonoid with antioxidant properties, have shown potential in managing diabetic complications. This study was aimed at investigating the therapeutic efficacy of these treatments, individually or in combination, against streptozotocin (STZ)-induced diabetic complications in albino rats ( Rattus norvegicus ). Methods: Diabetes was induced by intraperitoneal injection of STZ at 55 mg/kg in Wistar rats of both sexes weighing 200–250 g. Rats with serum glucose (Glu) levels ≥250 mg/dL were selected for pharmacological assessment. The diabetic rats were divided into six groups, each comprising six rats, receiving the following treatments: GLP alone at 0.5 mg/kg, rutin alone at 50 mg/kg or 100 mg/kg, and combinations of GLP with rutin. Treatments were administered over 45 days. Physiological parameters, serum markers (including Glu and lipid profiles), inflammatory cytokines, renal hypertrophy, oxidative stress markers, and histopathological changes in kidney tissues were evaluated to assess treatment effects. Result: Significant improvements were observed in rats treated with GLP, rutin, or both, including decreased diabetes-induced weight loss, and increased glycemic control with lower serum Glu levels. Favorable changes in lipid profiles and significant decreases in inflammatory cytokines indicated systemic improvements. Moreover, the treatments markedly decreased renal hypertrophy, thus suggesting enhanced renal function. Histopathological analysis indicated that combination therapy, compared with individual treatments, markedly decreased tubular dilation and preserved renal architecture, thus highlighting synergistic benefits in managing diabetic complications, particularly diabetic nephropathy. Conclusion: Our findings suggest that GLP and rutin, individually or in combination, hold promise in managing diabetic nephropathy, according to an STZ-induced diabetic rat model. The combination therapy demonstrated synergistic benefits, particularly in preserving renal architecture and decreasing tubular dilation. These results highlight a potential therapeutic strategy for alleviating diabetes-induced renal complications, and emphasize the importance of exploring combined approaches in diabetic management to enhance treatment efficacy and patient outcomes.

Vinod A. Bairagi

Shekhar D. Jagtap

Swapnil B. Jadhav

Smruti R. Jadhav

Yogesh S. Ahire

Rutin and Glimepiride Combination: A Novel Approach for Managing Diabetes Nephropathy in Streptozotocin Induced Diabetes in Wistar Rats

槲皮素与格列美脲联合应用：一种治疗链脲佐菌素诱导的Wistar大鼠糖尿病肾病的新方法

Abstract Background: Plasmodium falciparum is a malaria-causing unicellular parasite with strain 3D7 ( Pf 3D7) being the most lethal. Currently, antimalarial resistance has been reported which necessitates the development of novel antimalarial drugs to combat the spread of malaria. Garcinia atroviridis Griff. ex T. Anders contains phytochemical compounds that are useful for various activities, including targeting Pf 3D7 proteins. This study explored novel antimalarial drugs from G. atroviridis against several target proteins of Pf 3D7 in silico . Methods: Phytocompounds from G. atroviridis were selected as ligands. After retrieval from the Protein Data Bank, the protein sequence was screened using BLASTp NCBI. Molecular docking analysis was performed on PyRx to compute binding affinity and identify the chemical interactions involved. The stability of the ligand-protein complex was evaluated using dynamic molecular approaches. Results: Our findings showed that quercetin has a high binding affinity with apicoplast DNA polymerase (−8.3 kcal/mol), glutamyl-tRNA synthetase (−7.5 kcal/mol), and plasmepsin X (−7.8 kcal/mol). Kaempferol had a high binding affinity for the cytochrome c2 domain-swapped dimer (−8.4 kcal/mol). Conclusion: Collectively, quercetin and kaempferol are potential antimalarial candidates which warrant further investigation using in vitro and in vivo designs.

Nur Sofiatul Aini

Arif Nur Muhammad Ansori

Mochammad Aqilah Herdiansyah

Viol Dhea Kharisma

Muhammad Hermawan Widyananda

Ahmad Affan Ali Murtadlo

Dora Dayu Rahma Turista

Teguh Hari Sucipto

Sukma Sahadewa

Fara Disa Durry

Vikash Jakhmola

Maksim Rebezov

Valery P. Kartashev

Kadek Rachmawati

Putu Angga Wiradana

T. Karpagam

Hery Purnobasuki

Antimalarial Potential of Phytochemical Compounds from Garcinia atroviridis Griff ex. T. Anders Targeting Multiple Proteins of Plasmodium falciparum 3D7: An In Silico Approach

抗疟潜力：基于计算机模拟的Garcinia atroviridis Griff ex. T. Anders植物化学成分靶向恶性疟原虫3D7多重蛋白质的研究

Abstract Liquid smoke, a product of the pyrolysis process, includes components such as phenol, furfural, and ketones, and has acidic characteristics. Liquid smoke from various biomass sources has been used as a natural preservative worldwide and reported to be safe in humans. As a bio-economic product, liquid smoke has human health benefits. This review analyzes and describes the health benefits of liquid smoke from various biomass sources, according to in silico, in vitro, and in vivo studies. A systematic review following PRISMA guidelines was conducted to identify published reports of liquid smoke from various biomass sources. The anti-inflammatory, anti-bacterial, anti-diabetic, wound healing, and anti-periodontitis activity of liquid smoke was analyzed. Prior research has investigated liquid smoke produced through pyrolysis of various biomass types, such as rice husks ( Oryza sativa ), coconut shells ( Cocos nucifera L. ), palm kernels ( Elaeis guineensis Jacq . ), cocoa pods ( Theobroma cacao L .), tian op, and hickory ( Carya tomentosa (Lam.) Nutt .), as well as commercial liquid smoke. Toxicity testing, and in vitro and in vivo studies, are required for the assessment of health benefits. Therapeutic benefits of liquid smoke including anti-oxidant, anti-inflammatory, anti-nociceptive, anti-bacterial, anti-fungal, and anti-viral activity have been described. Further health benefits include anti-diabetic, anti-periodontitis, wound healing, and ulcer healing activity. These findings increase the use value of liquid smoke as a natural product with human health benefits.

Meircurius Dwi Condro Surboyo

Saeid Baroutian

Widyah Puspitasari

Ummi Zubaidah

Pamela Handy Cecilia

Dieni Mansur

Benni Iskandar

Nurina Febriyanti Ayuningtyas

Fatma Yasmin Mahdani

Diah Savitri Ernawati

Health benefits of liquid smoke from various biomass sources: a systematic review

不同生物质来源液态烟的健康益处：系统综述

Abstract Although diamond-like carbon-coated joint replacements are widely recommended for full bone replacements in humans, their clinical application is substantially limited by contamination with wear particles, specifically graphite nanoparticles, which are cytotoxic. This study was aimed at assessing the adverse effects of graphite oxide (GO) sheets on the blood and renal tissues of adult male albino rats. A total of 25 albino rats were procured from the Government College University Faisalabad, Punjab, Pakistan, and acclimated for 7 days in well-ventilated enclosures, after approval from the ethical committee at the University of Sialkot. The rats were randomly assigned to the following groups: a control group receiving no treatment, a vehicle control group receiving normal saline, and three treatment groups (G1, G2, and G3, administered GO nanosheets at doses of 5, 6, or 7 mg/kg body weight, respectively). Treatments were delivered through intraperitoneal injection on alternating days over 28 days. Animal mortality, hematological parameters, and kidney histology were assessed. The control and vehicle control groups showed normal findings, whereas the groups exposed to GO exhibited highly significant pathological changes in renal function tests ( p &lt;0.05). Histological alterations were more severe in the moderate- and high-dose treatment groups than the low-dose group, which displayed typical histological features. The treatment groups exhibited various histological changes, including vacuolation, renal fibrosis, inflammation, and tubular damage, which were significantly more pronounced in the G2 and G3 groups than the G1 group. Thus, exposure to GO sheets resulted in detrimental effects on renal tissues in albino rats. The findings suggested that the investigated doses of GO have detrimental effects on the health of living organisms.

Ambar N. Muhammad

Ayesha Ijaz

Adeel Khalid

Khuram Rafique

Rabia Tabassum

Aqeela Zahra

Muhammad Danish

Hina Tariq

Mochammad A. Herdiansyah

Arif N. M. Ansori

Renal Effects of Graphite Oxide Sheets in Albino Rats (Rattus norvegicus): A Preliminary Study

白化大鼠（褐家鼠）中氧化石墨烯片的肾脏效应：一项初步研究

ISSN	2712-0074, 2712-0082
h-index	12

Publication Information	Publisher: Compuscript Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2020，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

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Understanding of the Entry Mechanism of Nanoparticles into Tumors Determines the Future Direction of Nanomedicine Development

Non-Invasive Physical Stimulation to Modulate the Tumor Microenvironment: Unveiling a New Frontier in Cancer Therapy

Copper-Based Nanomaterials for Image-Guided Cancer Therapy

Exploring the Frontier of Inhalation Therapy: A Review of Dry Powder Inhalers for Precision Management of Inflammatory Lung Diseases

Rutin and Glimepiride Combination: A Novel Approach for Managing Diabetes Nephropathy in Streptozotocin Induced Diabetes in Wistar Rats

Exploring the Frontier of Inhalation Therapy: A Review of Dry Powder Inhalers for Precision Management of Inflammatory Lung Diseases

Rutin and Glimepiride Combination: A Novel Approach for Managing Diabetes Nephropathy in Streptozotocin Induced Diabetes in Wistar Rats

Antimalarial Potential of Phytochemical Compounds from Garcinia atroviridis Griff ex. T. Anders Targeting Multiple Proteins of Plasmodium falciparum 3D7: An In Silico Approach

Health benefits of liquid smoke from various biomass sources: a systematic review

Renal Effects of Graphite Oxide Sheets in Albino Rats (Rattus norvegicus): A Preliminary Study