STING deficiency alleviates ferroptosis through FPN1 stabilization in diabetic kidney disease.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has known as one of the most significant pathological processes involved in diabetic kidney disease (DKD). Stimulator of interferon genes (STING) has been demonstrated its potential in regulating ferroptosis, but the regulatory role in DKD mice and underlying mechanisms haven't been illustrated. To elucidate whether and how STING regulates ferroptosis in DKD, we detected the influence of STING on diabetic-related ferroptosis in a diabetic model and in erastin-induced renal tubular epithelial cells (RTECs). Our study demonstrated that STING was abnormally activated and promoted ferroptosis in DKD. STING deficiency alleviated renal pathologic damages and disfunction in diabetic mice via alleviating ferroptosis and reducing oxidative stress. Mechanismly, STING inhibition was shown to improve ferroptosis and reduce oxidative stress in erastin-induced RTECs. The disruption of ferroportin1 (FPN1) on the basis of STING inhibition abolished the improvements in ferroptosis and promoted reactive oxygen species (ROS) generation. Further, STING inhibition alleviated ferroptosis via stabilizing FPN1 protein level by decreasing ubiquitinated FPN1 for proteasomal degradation. In conclusion, STING deficiency protected against diabetic renal injury via alleviating ferroptosis through stabilizing FPN1 and reducing oxidative stress, providing a possible potential approach for the treatment of DKD.

Stimulator of interferon genes promotes diabetic sarcopenia by targeting peroxisome proliferator activated receptors γ degradation and inhibiting fatty acid oxidation.

BACKGROUND: Declined skeletal muscle mass and function are inevitable consequences of long-term diabetes and bring about many adverse events. Muscle fibre atrophy and interstitial fibrosis are major pathological manifestations of diabetic sarcopenia. Stimulator of interferon genes (STING) participates in various metabolic diseases. We aimed to explore whether and how STING regulates the above pathological manifestations of diabetic sarcopenia. METHODS: Wild-type and STINGgt/gt C57BL/6J mice and C2C12 myotubes were used to study the role of STING in the regulation of diabetic sarcopenia and the underlying mechanisms. RESULTS: STING was abnormally activated in diabetic muscles and in PA-treated myotubes (P < 0.01 for all parameters). The diabetic mice demonstrated decreased forelimb grip strength, lean mass, muscle weight and hanging impulse, which were improved by STING deficiency due to alleviated muscle fibre atrophy and interstitial fibrosis (P < 0.05 for all parameters). STING deficiency alleviated muscle fibre atrophy through the following mechanisms. Firstly, STING deficiency or inhibition increased the contents of pDRP1Ser616 , PINK1, Parkin and LC3-II, decreased p62 content, and increased the amount of mito-Keima fluorescent dots at 578 nm in diabetic state (P < 0.05 for all parameters), suggesting improved mitofission and mitophagy. Secondly, STING deficiency or inhibition increased the expression of pAKTSer473 and GLUT4 post-insulin change in diabetic state (P < 0.05 for all), indicating alleviated insulin resistance (IR). Mechanically, STING deficiency or inhibition increased peroxisome proliferator activated receptors γ (PPARγ) protein content by reducing the degradation of ubiquitinated PPARγ through the proteasome pathway and thus increased the expression of fatty acid oxidation (FAO)-related proteins in diabetic state (P < 0.05 for all parameters). Decreased expression of FAO-related proteins caused by PPARγ inhibition abolished the improvements in mitofission, mitophagy and IR achieved by STING inhibition in PA-treated myotubes and thus promoted muscle fibre atrophy (P < 0.05 for all parameters). STING deficiency alleviated interstitial fibrosis by decreasing TGFß1 expression in diabetic state and TGFß1 promoted the fibrogenic differentiation of fibro-adipogenic progenitors (P < 0.05 for all parameters). PPARγ inhibition abolished the effect of STING inhibition on reducing TGFß1 content in PA-treated myotubes (P < 0.01). CONCLUSIONS: STING deficiency exerted protective effects in diabetic sarcopenia by inhibiting the degradation of ubiquitinated PPARγ through the proteasome pathway and enhancing PPARγ-mediated FAO, which alleviated muscle fibre atrophy by promoting mitophagy and ameliorating IR, and alleviated interstitial fibrosis by reducing TGFß1 production and suppressing the fibrogenic differentiation of fibro-adipogenic progenitors.

Qualitative and quantitative features of deep endometriosis in contrast-enhanced ultrasound: An initial experience and literature review.

PURPOSE: This research aims to present the findings of contrast-enhanced ultrasound (CEUS) in a series of patients with proven deep endometriosis (DE) and provide an updated literature review. MATERIALS AND METHODS: Between January 2018 and October 2022, seven patients with DE lesions had their imaging and medical records retrospectively reviewed. Clinical data, recorded images of a standardized conventional B-mode ultrasound, and Sonovue® CEUS were interpreted by two blinded, independent, experienced radiologists in consensus. The enhanced characteristics of the DE lesion on CEUS were also assessed using VueBox® software quantitatively. RESULTS: DE lesion appeared as irregular hypoechoic or heterogeneous on conventional ultrasound with dotted blood flow signal on color Doppler. Six of seven DE lesions showed heterogeneous hypo-enhancement in arterial phases. All the lesions showed a heterogeneous washout rapidly that began in the late arterial phase. In quantified analysis, the mean relative peak enhancement compared with adjacent tissue was 0.47±0.25. CONCLUSION: Our findings and literature review suggested that CEUS could be a feasible and promising non-invasive modality for diagnosing DE.

Chemical fingerprints and implicated cancer risks of Polycyclic aromatic hydrocarbons (PAHs) from fine particulate matter deposited in human lungs.

Exposure to fine particles (PM2.5) and associated PAHs are frequently linked with lung cancer, which makes the understanding of their occurrence and health risk in human lungs urgently important. Using the ultrasonic treatment and sequencing centrifugation (USC) extraction method coupled with gas chromatography-tandem mass spectrometry (GC - MS/MS) analysis, we revealed the molecular fingerprints of PM-accumulated PAHs in human lungs from a cohort of 68 patients with lung cancer in a typical air-polluted region, China. Sixteen priority PAHs can be grouped by concentrations as âˆ¼ 1 × 104 ng/g (ANT/BkF/ACE/DBA/BgP/PHN/PYR), 2-5 × 103 ng/g (BaP/FLE/NaP/BbF), and âˆ¼ 1 × 103 ng/g (IND/Acy/CHR/FLT/BaA). The sum concentration of 16 PAHs was approximately equaled to 13% of those in atmospheric PM2.5, suggesting significant pulmonary leaching of PAHs deposited in lungs. Low- and high-molecular weight PAHs accounted for âˆ¼ 41.8% and âˆ¼ 45.1% of the total PAHs, respectively, which indicated that atmospheric PM2.5, tobacco and cooking smoke were likely to be important sources of pulmonary PAHs. The evident increasing concentrations of NaP and FLE in pulmonary PM were significantly correlated with smoking history among smokers. The implicated carcinogenic potency of PM-accumulated PAHs among the participants aged 70-80 was 17 times that among participants aged 40-50 on the basis of BaP equivalent concentration (BaPeq) evaluation. The particulate enrichment factor (EFP), the PAH content in pulmonary PM relative to the bulk lung tissue, was equaled to 54 âˆ¼ 835 and averaged at 436. The high value of EFP suggested that PAHs were essentially accumulated in pulmonary PM and exhibited a pattern of "hotspot" distribution in the lungs, which would likely increase the risk of monoclonal tumorigenesis. The chemical characteristics of PM-accumulated PAHs in human lungs together with their implicated lung cancer risks could provide significant information for understanding health effects of particulate pollution in the human body.

Utility of Sonazoid-Enhanced Ultrasound for the Macroscopic Classification of Hepatocellular Carcinoma: A Meta-analysis.

We assessed the diagnostic value of Sonazoid-enhanced ultrasound (SEUS) in determining the macroscopic classification of hepatocellular carcinoma (HCC) because of its strong relevance to the poor prognosis of the non-simple nodular (non-SN) type. The PubMed, EMBASE, Web of Science and Cochrane Library databases were searched for studies investigating patients who underwent surgery for HCC after undergoing SEUS pre-operatively. Five studies involving a total of 334 patients met the inclusion criteria. The summary sensitivity and specificity were 0.74 (95% confidence interval [CI]: 0.63-0.83) and 0.92 (95% CI: 0.82-0.97), respectively. The positive and negative likelihood ratios of SEUS for determining the macroscopic classification of HCC in Kupffer phase were 9.21 (95% CI: 4.02-21.13) and 0.28 (95% CI: 0.19-0.41), respectively. The diagnostic odds ratio of SEUS for determining the macroscopic classification of HCC was 34.2 (95% CI: 11.64-100.51), and the area under the summary receiver operating characteristic curve was 0.87 (95% CI: 0.84-0.90). Subgroup analysis suggested that small HCCs (≤30 mm) and studies including fewer than 70 patients may be associated with a higher diagnostic odds ratio than the corresponding subsets. SEUS had moderate diagnostic value for determining the macroscopic classification of HCC in the Kupffer phase.

Extracting keyframes of breast ultrasound video using deep reinforcement learning.

Ultrasound (US) plays a vital role in breast cancer screening, especially for women with dense breasts. Common practice requires a sonographer to recognize key diagnostic features of a lesion and record a single or several representative frames during the dynamic scanning before performing the diagnosis. However, existing computer-aided diagnosis tools often focus on the final diagnosis process while neglecting the influence of the keyframe selection. Moreover, the lesions could have highly-irregular shapes, varying sizes, and locations during the scanning. The recognition of diagnostic characteristics associated with the lesions is challenging and also faces severe class imbalance. To address these, we proposed a reinforcement learning-based framework that can automatically extract keyframes from breast US videos of unfixed length. It is equipped with a detection-based nodule filtering module and a novel reward mechanism that can integrate anatomical and diagnostic features of the lesions into keyframe searching. A simple yet effective loss function was also designed to alleviate the class imbalance issue. Extensive experiments illustrate that the proposed framework can benefit from both innovations and is able to generate representative keyframe sequences in various screening conditions.

ZIP12 Contributes to Hypoxic Pulmonary Hypertension by Driving Phenotypic Switching of Pulmonary Artery Smooth Muscle Cells.

ABSTRACT: ZIP12, a plasmalemmal zinc transporter, reportedly promotes pulmonary vascular remodeling (PVR) by enhancing proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms of ZIP12 facilitating PASMCs proliferation remain incompletely appreciated. It has been acknowledged that proliferation-predisposing phenotypic switching of PASMCs can lead to PVR. Given that hypoxia triggers phenotypic switching of PASMCs and ZIP12 mediates PVR, this study aims to explore whether ZIP12-mediated phenotypic switching of PASMCs contributes to hypoxia-induced PVR. Rats were exposed to hypoxia (10% O2) for 3 weeks to induce PVR, and primary rat PASMCs were cultured under hypoxic condition (3% O2) for 48 hours to induce proliferation. Immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis were performed to detect the expression of target mRNAs and proteins. EdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay were conducted to measure the proliferation of PASMCs. Hypoxia upregulated ZIP12 expression (both mRNA and protein) in pulmonary arteries and PASMCs. Knockdown of ZIP12 inhibited phenotypic switching of PASMCs induced by hypoxia. We propose that HIF-1α/ZIP12/pERK pathway could represent a novel mechanism underlying hypoxia-induced phenotypic switching of PASMCs. Therapeutic targeting of ZIP12 could be exploited to treat PVR.

Hv1 proton channel possibly promotes atherosclerosis by regulating reactive oxygen species production.

Atherosclerosis and its fatal complications, such as myocardial infarction or stroke, represent the most common cause of morbidity or mortality in modern world. It was observed that an excess of reactive oxygen species (ROS) accompanies atherosclerosis. Under physiological circumstances, intracellular H+ accumulates and cell membrane depolarizes during ROS production, rendering ROS generation self-limiting and thus avoiding oxidative stress. However, the persistent production of ROS during atherosclerosis suggests that the physiologically self-limiting ROS-generating process was somehow disrupted and there may be an as-yet unknown mechanism supporting unlimited ROS generation. We thus postulated that an outward H+ conductance, which can efficiently export H+ from the cytosol and maintain membrane potential, may play a crucial role during atherosclerosis. So far, Hv1 channels were mainly found in immune cells (macrophages, neutrophils). As large quantities of vascular infiltrating macrophages exist, we proposed that Hv1-mediated oxidative stress promoted excessive ROS production and the formation of foam cells, contributing to atherosclerosis. In addition, we could not exclude the possibility that Hv1 channels may be upregulated in vascular cells under atherosclerotic conditions, which may also exert effects on vascular inflammation and fibrous cap formation. The present study will employ Hv1 knockout mice in combination with in vitro studies to explore the role of Hv1 channel in atherosclerosis and dissect the underlying mechanisms. The results are expected to offer novel insights into the pathogenesis of atherosclerosis as well as clues for developing novel therapeutic avenues.

Preparation and application of subdivided tablets using 3D printing for precise hospital dispensing.

This study aimed to use three-dimensional printing technology to provide patients with accurate, safe and convenient subdivided drugs and bring the transformation of subdivided drugs' fabrication in the hospital. The formulation, preparation process, model and printing parameters, relationship between dose and preset model for printing of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg subdivided tablets prepared by three-dimensional printers were investigated in the study. The three-dimensional printed material consists of commercial tablets powders and other excipients, including lactose, corn starch, microcrystalline cellulose, and so on. Mass variation, drug content and drug content uniformity of subdivided tablets obtained by three-dimensional printing were compared with the pharmacists splitting subdivided tablets. Besides, the results from fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction confirmed that the preparation process of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg did not change the crystal structure of the active pharmaceutical ingredient. Furthermore, mass variation, drug content range and drug content uniformity of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg tablets split by pharmacists failed to comply with European Pharmacopoeia and Chinese Pharmacopoeia, while those of the three-dimensional printed subdivided tablets did. After the review of the ethics committee as a new technology for hospital dispensing, three-dimensional printed spironolactone subdivided tablets of 2 mg have been used in clinical inpatients and was accepted by pharmacists, nurses and patients. Compared with tablets subdivided split by pharmacists, three-dimensional printed spironolactone tablets of 2 mg were more accurate, safer and more customized, which indicated considerable potential in using three-dimensional printing technology as a new method for hospital dispensing.

Mediastinal hemangiomas: Spectrum of CT and MRI findings - retrospective case series study and systematic review of the literature.

PURPOSE: To analyze the imaging manifestations of mediastinal hemangioma (MH) by CT and MRI to aid in its successful diagnosis and preoperative evaluation. METHODS: Seventeen cases of MH diagnosed by histopathology combined with CT and MRI were retrospectively collected; and their CT and MRI features, including the lesions' site and range, shape, size, margin, density or signal, enhancement pattern, mass-cardiovascular interface, mass-pulmonary interface, and other characteristics were evaluated. RESULTS: The anterior, middle, and posterior mediastinum were involved in 13, 13, and 8 cases, respectively. The masses size varied from 20 to 233 mm. Irregular, dumbbell-like, and oval masses were found in 13, 2, and 2 cases, respectively, while with pampiniform growth in 16 cases and expansive growth in 1 case. Mixed density, homogeneous density solid masses, and heterogeneous density masses with dominant fat were found in 9, 5, and 3 cases, respectively, showing mild or significant enhancement in aortic phase while no or mild enhancement in pulmonary artery phase. Draining veins were found in 16 cases and feeding arteries in 10 cases. Phleboliths were detected in 10 cases, splenic hemangiomas in 6 cases, and left lateral-chest-wall hemangioma in 1 case. In MRI sequences, mixed signal was found on T1WI and heterogeneous hypersignal with nodular or linear hyposignal on T2WI in 5 cases, mild or significant enhancement in 4 cases, draining veins in 2 cases, and no feeding arteries or phleboliths were seen. CONCLUSION: Presence of phleboliths, pampiniform growth pattern, and aberrant draining veins are relatively specific characteristics in diagnosing MH.

Warpage optimization and influence factors analysis of 3D printing personalized JJY tablets.

To explore the feasibility of preparing traditional Chinese medicine using 3 D printing technology and reduce warpage commonly occurs in large-size tablets, we investigated the prescription, warpage optimization and influence factors of 3 D printing Jiuxiang Jianpi Yangwei (JJY) tablets. The procedures used conformed to the requirements of the 2015 edition of the Chinese Pharmacopeia. The results of the prescription screening showed that 75% ethanol and HPMC (9%) could be adhesives. Meanwhile, stevia (0.5%) and citric acid (0.5%) improved the taste of the 3 D printed JJY tablets. To ensure the quality and appearance of the printed tablets, the best parameters were as follows: drying at room temperature, 40% of the filling density, a 3 mm model height, two outer ring numbers and a printing speed of 15 mm/s. The optimized printed tablets had a smooth appearance, suitable hardness, with the weight uniformity in accordance with the Pharmacopeia. We also prepared personalized JJY cartoon tablets (which contained images of a big-headed pig and a small yellow duck) which were designed to increase the compliance of children when taking their medications. In conclusion, this study reported that 3 D printing technology has great potential for preparing traditional Chinese medicines, and it provided guidance for 3 D printing tablets without warpage.

Presarcopenia Is an Independent Risk Factor for Carotid Atherosclerosis in Chinese Population with Metabolic Syndrome.

PURPOSE: To investigate the impacts of skeletal muscle mass on carotid atherosclerosis in Chinese adults with metabolic syndrome (MetS). METHODS: One hundred and ninety-five subjects with MetS had the waist-to-height ratio (WHTR)≥0.5 for all. One hundred and eighty-four subjects without MetS were divided into 2 groups: Non-Mets obese group (WHTR ≥ 0.5, n = 118) and Non-MetS control group (WHTR < 0.5, n = 66). All the groups had no difference in age. Appendicular skeletal muscle mass was acquired and skeletal muscle mass index (SMI) was calculated. Carotid intima-media thickness (IMT) was assessed by ultrasonography. Each group was stratified according to the presence or absence of presarcopenia. RESULTS: While most parameters showed an increasing trend with WHTR and MetS in both genders, SMI and HDL-C showed a decreasing trend. The prevalence of carotid atherosclerosis showed the same increasing trend. Multivariate logistic regression analyses showed SBP and presarcopenia were both independent risk factors for carotid atherosclerosis in MetS (OR 1.026, P < 0.001; OR 2.788, P = 0.001, respectively). There was no significant difference in IMT among the three groups with preserved muscle mass whether the participants suffered from obesity or MetS, while there was a significant difference between the two groups with presarcopenia (in male P = 0.020, in female P = 0.009, respectively). The area under the ROC curve (AUC) was 0.641 (P<0.001) for presarcopenia. CONCLUSION: Obesity was a risk factor for sarcopenia independent of age, especially in subjects with metabolic syndrome. In individuals with MetS, our findings suggest that presarcopenia may be an independent risk factor for atherosclerosis and appendicular skeletal muscle mass had potential protective effects for carotid atherosclerosis regardless of gender.

Optimized preparation of vinpocetine micelles and in vivo evaluation of its pharmacokinetics in rats.

This study aimed to develop a novel monomethoxy poly(ethylene glycol)-b-poly(D, L-lactide) (mPEG5000-PLA10 000) micelle drug delivery system to improve vinpocetine's (VP) dissolution and sustain VP concentrations in plasma. Three micelle fabrication methods were examined to maximize VP loading, followed by structurally characterization and investigation in vitro release and in vivo pharmacokinetics in Sprague-Dawley rats. The thin-film hydration is the most appropriate method of the three methods because of its high loading content. The loaded micelles exhibited a sustained release behavior up to 48 h. Following intraperitoneal administration (9 mg/kg), VP loaded micelles provided significantly higher (335%) AUC (area under concentration-time) compared to VP injection. And also increased the mean residence time [MRT(0-t)] and elimination half-life (t1/2z). There were obviously two peaks at 2 h and 9 h in VP loaded micelles concentration-time profile. In summary, these data demonstrated that poly mPEG-PLA micelles can efficiently sustain VP concentrations in plasma for 36 h, thus apprehending polymeric micelles suitability as poor aqueous solubility drug carriers.

The Xc- inhibitor sulfasalazine improves the anti-cancer effect of pharmacological vitamin C in prostate cancer cells via a glutathione-dependent mechanism.

PURPOSE: Traditional treatment regimens for advanced prostate cancer, especially castration-resistant prostate cancer, result in low survival times with severe side effects. Therefore, new treatment options are required. Vitamin C (VC) has been identified as a promising anti-cancer agent of which the effects depend on the accumulation of H2O2 that is produced through autoxidation. Sulfasalazine (SAS), a cystine transporter (Xc-) inhibitor, is known to suppress cellular glutathione (GSH) biosynthesis. Here, we hypothesized that targeting the Xc- transporter via SAS may improve the anti-cancer activity of VC through regulating GSH biosynthesis, which in turn may result in the accumulation of reactive oxygen species (ROS). METHODS: The anti-cancer effect of VC and/or SAS on prostate cancer cells was assessed using WST-8, colony formation and annexin V-FITC/PI FACS assays. Changes in cellular ROS and GSH levels were determined to verify our hypothesis. Finally, BALB/c nude mice bearing prostate cancer xenografts were used to assess the anti-cancer effects of single or combined VC and SAS therapies. RESULTS: We found that SAS could potentiate the short- and long-term cytotoxicity of VC in prostate cancer cells. We also found that the synergistic effect of SAS and VC led to significant cellular GSH depletion, resulting in increased ROS accumulation. This synergistic effect could be reversed by the antioxidant N-acetyl-L-cysteine (NAC). The synergistic effect of SAS and VC was also noted in prostate cancer xenografts and correlated with immunohistochemistry results. CONCLUSIONS: Our results strongly indicate that SAS, a relatively non-toxic drug that targets cystine transporters, in combination with VC may be superior to their single applications in the treatment of prostate cancer.

A Modular Strategy to Engineer Complex Tissues and Organs.

Currently, there are no synthetic or biologic materials suitable for long-term treatment of large tracheal defects. A successful tracheal replacement must (1) have radial rigidity to prevent airway collapse during respiration, (2) contain an immunoprotective respiratory epithelium, and (3) integrate with the host vasculature to support epithelium viability. Herein, biopolymer microspheres are used to deliver chondrogenic growth factors to human mesenchymal stem cells (hMSCs) seeded in a custom mold that self-assemble into cartilage rings, which can be fused into tubes. These rings and tubes can be fabricated with tunable wall thicknesses and lumen diameters with promising mechanical properties for airway collapse prevention. Epithelialized cartilage is developed by establishing a spatially defined composite tissue composed of human epithelial cells on the surface of an hMSC-derived cartilage sheet. Prevascular rings comprised of human umbilical vein endothelial cells and hMSCs are fused with cartilage rings to form prevascular-cartilage composite tubes, which are then coated with human epithelial cells, forming a tri-tissue construct. When prevascular- cartilage tubes are implanted subcutaneously in mice, the prevascular structures anastomose with host vasculature, demonstrated by their ability to be perfused. This microparticle-cell self-assembly strategy is promising for engineering complex tissues such as a multi-tissue composite trachea.

Cytocompatible Catalyst-Free Photodegradable Hydrogels for Light-Mediated RNA Release To Induce hMSC Osteogenesis.

Macroscopic hydrogels provide valuable platforms for controlling the release of genetic materials such as small interfering RNA (siRNA) and microRNA (miRNA) for biomedical applications. However, after these hydrogels are formed, it is challenging to alter the release rate of genetic materials. In this report, a Michael addition catalyst-free photodegradable poly(ethylene glycol) (PEG)-based hydrogel system has been developed that provides an active means of controlling the release of genetic materials postgelation using external UV light application. Photodegradation of photolabile linkages in the hydrogel network changes the hydrogel physiochemical properties such as swelling and degradation rate, augmenting the release rate of loaded genetic materials. In the absence of UV light, RNAs were released in a sustained fashion from both photodegradable and nonphotodegradable hydrogels. In contrast, RNA release rate from the photodegradable hydrogels was accelerated via UV light application, whereas it was not elevated with nonphotodegradable hydrogels. Regardless of the UV light exposure to the hydrogels, released siRNA against green fluorescent protein (siGFP) retained its bioactivity via effectively silencing GFP expression in destabilized GFP (deGFP)-expressing HeLa cells cultured in monolayer. Moreover, cells encapsulated in these hydrogels exhibited high cell viability, and loaded siGFP inhibited GFP expression of encapsulated deGFP-expressing HeLa cells with or without UV light application to the hydrogels. Importantly, released siRNA targeting noggin (siNoggin) and miRNA-20a from the hydrogels, with and without UV light application, induced osteogenic differentiation of human mesenchymal stem cells (hMSCs). This photodegradable hydrogel system may be a promising strategy for real-time, user-controlled release of genetic materials for tissue engineering and treatment of diseases such as cancer.