Effects of telmisartan on fat distribution: a meta-analysis of randomized controlled trials

<p><b>Objectives</b>: Several meta-analyses have confirmed the positive metabolic effects of telmisartan, an angiotensin II receptor blocker that can also act as a partial peroxisome proliferator-activated receptor-γ agonist, compared to those of other angiotensin II receptor blockers. These effects include decreased fasting glucose, glycosylated hemoglobin, interleukin-6, and tumor necrosis factor-α levels. However, no systemic analysis of telmisartan’s effects on body fat distribution has been performed. We performed a meta-analysis of randomized controlled telmisartan trials to investigate its effects on body weight, fat distribution, and visceral adipose reduction. <b>Research design and methods</b>: A literature search was performed using Embase, MEDLINE, and the Cochrane Library between January 1966 and November 2013. Randomized controlled trials in English and meeting the following criterion were included: random assignment of hypertensive participants with overweight/obesity, metabolic syndrome, or glucose intolerance to telmisartan or control therapy group. <b>Results</b>: Of 651 potentially relevant reports, 15 satisfied the inclusion criterion. While visceral fat area was significantly lower in the telmisartan group than in the control group (weighted mean difference = −18.13 cm², 95% C.I. = −27.16 to −9.11, <i>P_χ</i>² = 0.19, <i>I</i>² = 41%), subcutaneous fat area was similar (weighted mean difference =2.94 cm², 95% C.I. = −13.01 to 18.89, <i>P_χ</i>² = 0.30, <i>I</i>² = 17%). Total cholesterol levels were significantly different between the groups (standardized mean difference = −0.24, 95% C.I. = −0.45 to −0.03, <i>P_χ</i>² = 0.0002, <i>I</i>² = 67%). <b>Limitations</b>: Limitations include: (1) limited number of studies, especially those evaluating fat distribution; (2) different imaging modalities to assess visceral fat area (V.F.A.) and subcutaneous fat area (S.F.A.); (3) observed heterogeneity. <b>Conclusion</b>: The findings suggest that telmisartan affected fat distribution, inducing visceral fat reduction, and thus could be useful in hypertensive patients with obesity/overweight, metabolic syndrome, or glucose intolerance.</p

An Activatable Prodrug for the Treatment of Metastatic Tumors

Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H₂O₂), supporting the hypothesis that a prodrug could be activated by intracellular H₂O₂ and lead to a potential antimetastatic therapy. In this study, prodrug <b>7</b> was designed to be activated by H₂O₂-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug <b>7</b> was investigated by monitoring fluorescence after addition of H₂O₂ to the cancer cells. Prodrug <b>7</b> activated by H₂O_2, selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug <b>7</b> showed effective antitumor activity in a mouse model of metastatic lung disease. Thus, this H₂O₂-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anticancer drug, SN-38

Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections

The impact of bacteria on cancer progression and treatment is becoming increasingly recognized. Cancer-associated bacteria are linked to metastases, reduced efficacy, and survival challenges. In this study, we present a sensitive hypoxia-activated prodrug, NR-NO2, which comprises an antibiotic combined with a chemotherapeutic. This prodrug demonstrates rapid and robust fluorescence enhancement and exhibits potent antibacterial activity against both Gram-positive and Gram-negative bacteria as well as tumor cells. Upon activation, NR-NO2 produces a distinct “fluorescence-on” signal, enabling real-time drug release monitoring. By leveraging elevated nitroreductase in cancer cells, NR-NO2 gives rise to heightened bacterial cytotoxicity while sparing normal cells. In A549 solid tumor-bearing mice, NR-NO2 selectively accumulated at tumor sites, displaying fluorescence signals under hypoxia superior to those of a corresponding prodrug-like control. These findings highlight the potential of NR-NO2 as a promising cancer therapy prodrug that benefits from targeted release, antibacterial impact, and imaging-based guidance

Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections

The impact of bacteria on cancer progression and treatment is becoming increasingly recognized. Cancer-associated bacteria are linked to metastases, reduced efficacy, and survival challenges. In this study, we present a sensitive hypoxia-activated prodrug, NR-NO2, which comprises an antibiotic combined with a chemotherapeutic. This prodrug demonstrates rapid and robust fluorescence enhancement and exhibits potent antibacterial activity against both Gram-positive and Gram-negative bacteria as well as tumor cells. Upon activation, NR-NO2 produces a distinct “fluorescence-on” signal, enabling real-time drug release monitoring. By leveraging elevated nitroreductase in cancer cells, NR-NO2 gives rise to heightened bacterial cytotoxicity while sparing normal cells. In A549 solid tumor-bearing mice, NR-NO2 selectively accumulated at tumor sites, displaying fluorescence signals under hypoxia superior to those of a corresponding prodrug-like control. These findings highlight the potential of NR-NO2 as a promising cancer therapy prodrug that benefits from targeted release, antibacterial impact, and imaging-based guidance