The authors have no acknowledgments.

All procedures carried out in research involving human participants were in accordance with the approval of the Ethics Review Committee of the First Affiliated Hospital of Chongqing Medical University (Research Ethics in 2023 [2023-119]). Informed consent was obtained from the patients before undergoing the procedure.
1. Pretreatment preparation
<ol>
	<li>Lesion selection and clinical indications
	<ol>
		<li>Patient selection
		<ol>
			<li>Select female patients with Fitzpatrick skin type III-IV12 and clinical symptom quantitative score of facial aging &#62; 9 points13.</li>
			<li>Exclude patients who fall into any of these categories: pregnant and breastfeeding women; patients with a history of allergy to lidocaine and/or salicylic acid; patients with malignant tumors, scars, diabetes, neuromuscular diseases, bleeding tendency, anticoagulants, glucocorticoids or immunosuppressive drugs; patients who have received laser or other treatments within the past 6 months.</li>
		</ol>
		</li>
		<li>Patient preparation
		<ol>
			<li>After cleaning the patient&#39;s face, use the skin detector to perform a skin test.</li>
			<li>Then, apply the compound lidocaine cream externally to the treatment area and leave it for 40 min. Afterward, wash the entire face with water and dry it with sterile gauze.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>1565 nm non-ablative fractional laser device parameter settings.
	<ol>
		<li>Choose the 1565 nm non-ablative fractional laser device (ResurFX mode) (as shown in Figure 1) for comprehensive facial treatment on the patient.</li>
		<li>Set the energy level using the Energy Setting key, usually between 30-40 mJ, with the desired endpoint reaction being erythema and mild edema, which generally appear tens of seconds after treatment and, in rare cases, occur minutes later.</li>
		<li>Adjust the treatment density using the Density Setting key, usually between 200-300 spots/cm2, with the desired endpoint reaction being erythema and mild edema.</li>
	</ol>
	</li>
	<li>Have the patient lie comfortably on the treatment bed, with the doctor sitting at the head end of the bed. Disinfect the entire treatment area with iodophor, remove the iodine with sterile saline, and then dry the area with sterile gauze.</li>
	<li>Disinfect the treatment head of the device with a 75% alcohol pad. 
	NOTE: Both the doctor and the patient should wear specific protective goggles in preparation for the treatment.</li>
</ol>
2. Treatment
<ol>
	<li>Enter the treatment interface and select the ResurFX mode (as shown in Figure 2).
	<ol>
		<li>Choose the appropriate spot size and shape, and click Ready on the instrument interface (Figure 3). Gently place the treatment head on the skin surface of the treatment area and press the Trigger button on the treatment instrument to start the treatment.</li>
		<li>After the treatment prompt sound stops, release the Trigger button, lift the handle, and select the next treatment area for treatment. Ensure that the treatment spots do not overlap. Treat the entire face for 1 time.</li>
		<li>Keep the skin area dry during the treatment process. During each energy emission process, firmly adhere the treatment head to the skin surface.</li>
		<li>Test the spot at the lower jaw or in front of the ear first, with the endpoint reaction being redness and slight edema, before performing a large-area treatment. During the entire treatment process, cover the patient&#39;s eyes with an eye mask (provided by the instrument manufacturer) to protect the patient&#39;s eyes.</li>
	</ol>
	</li>
	<li>Perform non-ablative fractional laser treatment of the face with 1565 nm energy.
	<ol>
		<li>Minimize overlap between each spot. Different parts require different suitable parameters. For example, patients with Fitzpatrick III/IV generally require a treatment energy of 30-35 mJ and a density of 200-250 spots/cm2 for the forehead.</li>
		<li>Set the treatment energy for the cheek area to 35-40 mJ and the density to 200-250 spots/cm2. Set the treatment energy for the nose to 35-40 mJ and the density to 250-300 spots/cm2.</li>
		<li>After the entire face is treated, click Standby on the instrument treatment interface to place the instrument in standby mode.</li>
	</ol>
	</li>
	<li>Apply 30% supramolecular salicylic acid immediately after the whole-face laser treatment. 
	NOTE: The application order is generally forehead, nose, chin, cheeks, and temples.</li>
	<li>Gently massage for 5-10 min.
	<ol>
		<li>After evenly applying SSA to the entire face, gently massage in a circular motion with fingers wearing latex gloves to promote absorption. 
		NOTE: The specific reaction time depends on the appearance of the endpoint reaction, which is facial redness or white frost reaction.</li>
		<li>Rinse off with water immediately when the endpoint reaction appears. If the reaction time has reached 10 min but the end point reaction does not appear, rinse off with water immediately.</li>
	</ol>
	</li>
</ol>
3. Posttreatment care
<ol>
	<li>Apply cold saline gauze for 30 min immediately after treatment.</li>
	<li>Do not clean the face for 3 days after the treatment. Apply moisturizing and repairing products externally and pay attention to sun protection. 
	NOTE: After the treatment, there may be slight scabbing on the face. It is not recommended to use sunscreen and facial makeup before the scabs fall off. Items for physical sun protection, such as a mask, hat, or parasol, can be chosen. Patients must not wash their face for 3 days but could gently wipe it with normal saline.</li>
</ol>

Minimizing Pigmentation in Laser Treatment Using Salicylic Acid

<ol>
	<li>Ko, A. C., Korn, B. S., Kikkawa, D. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+aging+face.">The aging face.</a> Surv Ophthalmol. 62 (2), 190-202 (2017).</li><li>Khavkin, J., Ellis, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aging+skin:+histology,+physiology,+and+pathology.">Aging skin: histology, physiology, and pathology.</a> Facial Plast Surg Clin North Am. 19 (2), 229-234 (2011).</li><li>Horovitz, T., Clementoni, M. T., Artzi, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonablative+laser+skin+resurfacing+for+periorbital+wrinkling+-+A+case+series+of+16+patients.">Nonablative laser skin resurfacing for periorbital wrinkling - A case series of 16 patients.</a> J Cosmet Dermatol. 20 (1), 99-104 (2021).</li><li>Dou, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fractional+microneedle+radiofrequency+device+and+fractional+erbium-doped+glass+1,565-nm+device+treatment+of+human+facial+photoaging:+a+prospective,+split-face,+random+clinical+trial.">Fractional microneedle radiofrequency device and fractional erbium-doped glass 1,565-nm device treatment of human facial photoaging: a prospective, split-face, random clinical trial.</a> J Cosmet Laser Ther. 23 (5-6), 142-148 (2021).</li><li>Wang, Y., Zheng, Y., Cai, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+and+safety+of+1565-nm+non-ablative+fractional+laser+versus+long-pulsed+1064-nm+Nd:YAG+laser+in+treating+enlarged+facial+pores.">Efficacy and safety of 1565-nm non-ablative fractional laser versus long-pulsed 1064-nm Nd:YAG laser in treating enlarged facial pores.</a> Lasers Med Sci. 37 (8), 3279-3284 (2022).</li><li>Lin, A. N., Nakatsui, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salicylic+acid+revisited.">Salicylic acid revisited.</a> Int J Dermatol. 37 (5), 335-342 (1998).</li><li>Arif, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salicylic+acid+as+a+peeling+agent:+a+comprehensive+review.">Salicylic acid as a peeling agent: a comprehensive review.</a> Clin Cosmet Investig Dermatol. 8, 455-461 (2015).</li><li>Zhang, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=30%+supramolecular+salicylic+acid+peels+effectively+treats+acne+vulgaris+and+reduces+facial+sebum.">30% supramolecular salicylic acid peels effectively treats acne vulgaris and reduces facial sebum.</a> J Cosmet Dermatol. 21 (8), 3398-3405 (2022).</li><li>Zheng, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+and+safety+of+2%+supramolecular+salicylic+acid+compared+with+5%+benzoyl+peroxide/0.1%+adapalene+in+the+acne+treatment:+a+randomized,+split-face,+open-label,+single-center+study.">Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized, split-face, open-label, single-center study.</a> Cutan Ocul Toxicol. 38 (1), 48-54 (2019).</li><li>Han, Q., Zeng, J., Liu, Y., Yin, J., Sun, P., Wu, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+30%+supramolecular+salicylic+acid+followed+by+1565-nm+non-ablative+fractional+laser+on+facial+acne+and+subsequent+enlarged+pores.">Evaluation of 30% supramolecular salicylic acid followed by 1565-nm non-ablative fractional laser on facial acne and subsequent enlarged pores.</a> Lasers Med Sci. 38 (1), 91 (2023).</li><li>Salter, S. A., Kimball, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Striae+gravidarum.">Striae gravidarum.</a> Clin Dermatol. 24 (2), 97-100 (2006).</li><li>Li, Y. J. Z., Luo, S., Xu, K. X., Hao, L. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+observation+of+the+injection+of+autologous+concentrated+growth+factors+(CGF)+in+the+improvement+of+facial+inflammaging.">Clinical observation of the injection of autologous concentrated growth factors (CGF) in the improvement of facial inflammaging.</a> Chin J Aesth Plast Surg. 30 (4), 236-239 (2019).</li><li>Munavalli, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Split-face+assessment+of+the+synergistic+potential+of+sequential+Q-switched+Nd:YAG+laser+and+1565+nm+fractional+nonablative+laser+treatment+for+facial+rejuvenation+in+Fitzpatrick+skin+Type+II-V+patients.">A Split-face assessment of the synergistic potential of sequential Q-switched Nd:YAG laser and 1565 nm fractional nonablative laser treatment for facial rejuvenation in Fitzpatrick skin Type II-V patients.</a> J Drugs Dermatol. 15 (11), 1335-1342 (2016).</li><li>Chan, H. H., Manstein, D., Yu, C. S., Shek, S., Kono, T., Wei, W. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+prevalence+and+risk+factors+of+post-inflammatory+hyperpigmentation+after+fractional+resurfacing+in+Asians.">The prevalence and risk factors of post-inflammatory hyperpigmentation after fractional resurfacing in Asians.</a> Lasers Surg Med. 39 (5), 381-385 (2007).</li><li>Gold, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+future+of+non-invasive+rejuvenation+technology:+Devices.">The future of non-invasive rejuvenation technology: Devices.</a> J Drugs Dermatol. 16 (6), s104-s107 (2017).</li><li>Lu, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salicylic+acid+treats+acne+vulgaris+by+suppressing+AMPK/SREBP1+pathway+in+sebocytes.">Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes.</a> Exp Dermatol. 28 (7), 786-794 (2019).</li></ol>

The authors have nothing to disclose.

1565 nm non-ablative fractional laser can effectively stimulate collagen rearrangement, achieving the effect of rejuvenation and anti-aging. It is used in the treatment of facial rejuvenation, stretch marks, and acne scars14. However, after 1565 nm non-ablative fractional laser treatment, there may be obvious pain and redness immediately, and posttreatment inflammation pigmentation easily occurs, which makes it difficult for some patients to accept. In this article, we described an effective metho...

Facial aging usually refers to the changes that occur after aging, such as bone shrinkage and deformation, soft tissue relaxation and sagging, increased skin pigmentation, and wrinkles, among which the aging of the skin is the most obvious1. The causes of facial aging are divided into exogenous and endogenous factors. Exogenous aging is caused by gravity, UV radiation, air pollution, smoking, excessive alcohol consumption, and malnutrition, among other factors2. Endogenous aging is mainly an inevitable aging process caused by genetics and age. With the pursuit of a beautiful image by those seeking beauty, various technologies and treatment concepts have emerged. Among them, photonic beauty treatments have developed rapidly in the treatment of facial aging in recent years. According to statistics from the International Society of Aesthetic Plastic Surgery, the number of patients undergoing photonic beauty treatments in the United States in 2020 increased by 15.2% compared to 20193.
Currently, there are various laser devices available for treating skin aging. These lasers are primarily used to reduce wrinkles and improve enlarged pores and can be categorized as ablative or non-ablative lasers. Non-ablative lasers, such as different wavelengths of erbium-doped glass (Er:Glass) lasers (1540 nm, 1550 nm, 1565 nm), are representative instruments for this purpose, with the ResurFX fiber optic laser being the most commonly used. The 1565 nm laser emitted by ResurFX can stimulate dermal collagen remodeling while maintaining the integrity of the epidermis. It has shown good efficacy and high safety for the treatment of periorbital wrinkles4. A prospective study has confirmed that non-ablative fractional lasers can improve various facial skin concerns, such as laxity, wrinkles, and coarse pores, among Asian patients, and the patients were satisfied with the treatment outcomes5. However, posttreatment complications such as pain, erythema, edema, crust formation, inflammatory hyperpigmentation, and acne eruptions were reported in 100% of cases treated with non-ablative fractional lasers. Currently, in order to alleviate the adverse reactions during and after non-ablative fractional laser treatment, methods include a topical anesthetic ointment that can be applied before treatment to improve treatment tolerance, and an adequate cold compress after laser treatment can shorten the duration of erythema and edema6. However, these treatments have limited effects in reducing pain and erythema edema and still cannot make all patients accept non-ablative fractional laser treatment.
Salicylic acid (SA) is a &#946;-hydroxy acid extracted from willow bark, etc.7, with a concentration of 2% ~ 30%. SA can remove lipids between cells, reduce the adhesion of keratin-forming cells, and cause these cells to loosen and subsequently separate8. In addition, it has antibacterial, antifungal, and some anesthetic effects9. However, SA has poor solubility in water and easily precipitates in low-pH alcohol solutions and irritating solvents to the skin. To solve these limitations, supramolecular SA (SSA) was introduced. It forms water-soluble supramolecular entities in the form of intermolecular complexes through reversible non-covalent bonding and releases slowly during use, reaching maximum efficacy under low-pH conditions and reducing skin irritation10. Zhang et al.9. measured skin hydration, transepidermal water loss (TEWL), pH value of skin barrier-related parameters. After four treatments, TEWL decreased, while skin hydration and pH values increased. These results suggested that 30% of SSA peels did not damage the skin barrier function but improved instead.
Therefore, some scholars advocate the use of non-ablative fractional laser combined with SSA chemical peel treatment to improve problems such as large pores and acne11. However, according to the author's experience, the immediate use of SSA chemical peel treatment after 1565 nm non-ablative fractional laser treatment has not been fully utilized in clinical practice, which may be due to different treatment sequences in previous clinical practice. This article introduces a new treatment method to improve the adverse reactions after 1565 nm non-ablative fractional laser treatment, combined with relevant visual aids, in order to help more patients receive 1565 nm non-ablative fractional laser treatment for facial rejuvenation.

<table><tbody><tr><td>ResurFX fiber optic laser</td><td>Lumenis, Yokneam, Israel</td><td>M22 system</td><td>1565 nm non-ablative fractional laser</td></tr><tr><td>ISEMECO skin detector&amp;nbsp;</td><td>Isomeco Biomedical Technology Co., Ltd.,Shanghai, China</td><td>MC-2600</td><td>Skin testing can be conducted under 5 types of spectrum</td></tr><tr><td>Compound lidocaine cream</td><td>Beijing Unigroup Pharmaceutical Co., Ltd., China</td><td>Guo Yao Quan Zi H20063466</td><td>This product is a compound preparation, consisting of prilocaine and lidocaine. Each gram of this product contains 25 mg of prilocaine and 25 mg of lidocaine.</td></tr><tr><td>30% supramolecular salicylic acid</td><td>BRODA, Shanghai Ruizhi Medical Technology Co., Ltd., China</td><td>N/A</td><td>It can be used for anti-inflammatory and repairing the skin barrier.</td></tr></tbody></table>

enhancement of facial rejuvenation through a combination of 1565 nm non-ablative fractional laser with 30% supramolecular salicylic acid

The 1565 nm non-ablative fractional laser can effectively stimulate collagen regeneration, achieving the effect of skin rejuvenation and anti-aging. In recent years, it has been widely used in dermatology, especially in facial rejuvenation, treatment of stretch marks, and acne scar treatment, with significant results. However, after the 1565 nm non-ablative fractional laser treatment, patients may experience short-term erythema and edema. The inflammation after treatment may also cause pigmentation, making it difficult for some patients to accept. This article introduces a treatment method of 1565 nm non-ablative fractional laser combined with 30% super molecular salicylic acid for facial rejuvenation, effectively reducing posttreatment erythema and post-inflammatory pigmentation. The method includes specific treatment steps and the respective endpoint reactions of each step. The method starts by selecting appropriate energy parameters for the 1565 nm non-ablative fractional laser treatment, followed immediately by the application of 30% supramolecular salicylic acid. The treatment should be stopped when a frosty reaction occurs. The purpose of this project is to provide patients with a safer new method of facial rejuvenation treatment.

The 1565 nm non-ablative fractional laser can improve facial aging, such as pores, texture, and brown spots. However, the combination of a 1565 nm non-ablative fractional laser with SSA can effectively reduce adverse reactions such as erythema and pigmentation while improving facial aging. The right side of the patient&#39;s face was treated with a 1565 nm non-ablative fractional laser, while the left side was treated with a 1565 nm non-ablative fractional laser combined with 30% supramolecular salicylic acid. At 14 days...

Author Spotlight: Advancing Facial Rejuvenation Therapy with Post-Laser Salicylic Acid Application

The purpose of this project is to effectively reduce the occurrence of adverse reactions such as erythema and pigmentation after non-ablative fractional laser treatment by combining 1565 non-ablative fractional laser with 30% super molecular salicylic acid, providing patients with a safer new method of facial rejuvenation treatment.

Enhancement of Facial Rejuvenation Through a Combination of 1565 nm Non-Ablative Fractional Laser with 30% Supramolecular Salicylic Acid

The 1565 nm non-ablative fractional laser can effectively stimulate collagen regeneration, achieving the effect of skin rejuvenation and anti-aging. In ...

enhancement-facial-rejuvenation-through-combination-1565-nm-non

Research

JoVE Journal

Medicine

772 Views.  Chongqing Medical University. Mijn onderzoek richt zich op gezichtsverjonging en ik wil klinische ervaring vertalen naar evidence-based medische resultaten door middel van klinische studies. Momenteel hebben verschillende clinici het gebruik van 30%super moleculair salicylzuur geïmplementeerd onmiddellijk na 1.565 nanometer niet-ablatieve fractionele laserbehandeling, en ontdekten dat deze gecombineerde aanpak beter presteert dan de enige toepassing van 1565 nanometer niet-ablatieve frac...

Video: Auteur in de schijnwerpers: Bevordering van gezichtsverjongingstherapie met toepassing na lasersalicylzuur

Single Molecule Analysis of Laser Localized Psoralen Adducts

The DNA Damage Response (DDR) has been extensively characterized in studies of double strand breaks (DSBs) induced by laser micro beam irradiation in live cells. The DDR to helix distorting covalent DNA modifications, including interstrand DNA crosslinks (ICLs), is not as well defined. We have studied the DDR stimulated by ICLs, localized by laser photoactivation of immunotagged psoralens, in the nuclei of live cells. In order to address fundamental questions about adduct distribution and replication fork encounters, we combined laser localization with two other technologies. DNA fibers are often used to display the progress of replication forks by immunofluorescence of nucleoside analogues incorporated during short pulses. Immunoquantum dots have been widely employed for single molecule imaging. In the new approach, DNA fibers from cells carrying laser localized ICLs are spread onto microscope slides. The tagged ICLs are displayed with immunoquantum dots and the inter-lesion distances determined. Replication fork collisions with ICLs can be visualized and different encounter patterns identified and quantitated.

Lasers are frequently used in studies of the cellular response to DNA damage. However, they generate lesions whose spacing, frequency, and collisions with replication forks are rarely characterized. Here, we describe an approach that enables the determination of these parameters with laser localized interstrand crosslinks.

The DNA Damage Response (DDR) has been extensively characterized in studies of double strand breaks (DSBs) induced by laser micro beam irradiation in live ...

Genetics

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Breast cancer is one of the most common cancers amongst women in North America. Many current anti-cancer treatments, including ionizing radiation, induce apoptosis via DNA damage. Unfortunately, such treatments are non-selective to cancer cells and produce similar toxicity in normal cells. We have reported selective induction of apoptosis in cancer cells by the natural compound pancratistatin (PST). Recently, a novel PST analogue, a C-1 acetoxymethyl derivative of 7-deoxypancratistatin (JCTH-4), was produced by de novo synthesis and it exhibits comparable selective apoptosis inducing activity in several cancer cell lines. Recently, autophagy has been implicated in malignancies as both pro-survival and pro-death mechanisms in response to chemotherapy. Tamoxifen (TAM) has invariably demonstrated induction of pro-survival autophagy in numerous cancers. In this study, the efficacy of JCTH-4 alone and in combination with TAM to induce cell death in human breast cancer (MCF7) and neuroblastoma (SH-SY5Y) cells was evaluated. TAM alone induced autophagy, but insignificant cell death whereas JCTH-4 alone caused significant induction of apoptosis with some induction of autophagy. Interestingly, the combinatory treatment yielded a drastic increase in apoptotic and autophagic induction. We monitored time-dependent morphological changes in MCF7 cells undergoing TAM-induced autophagy, JCTH-4-induced apoptosis and autophagy, and accelerated cell death with combinatorial treatment using time-lapse microscopy. We have demonstrated these compounds to induce apoptosis/autophagy by mitochondrial targeting in these cancer cells. Importantly, these treatments did not affect the survival of noncancerous human fibroblasts. Thus, these results indicate that JCTH-4 in combination with TAM could be used as a safe and very potent anti-cancer therapy against breast cancer and neuroblastoma cells.

We have synthesized a novel analogue of pancratistatin with comparable anti-cancer activity as native pancratistatin; interestingly, combinatory treatment with tamoxifen yielded a drastic enhancement in apoptotic and autophagic induction by mitochondrial targeting with minimal effect on noncancerous fibroblasts. Thus, JCTH-4 in combination with tamoxifen could provide a safe anti-cancer therapy.

Breast cancer is one of the most common cancers amongst women in North America. Many current anti-cancer treatments, including ionizing radiation, induce ...

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using 'gold standard' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure&gt;150 mmHg), proteinuria (&gt; 50 mg/24 hr) and mild uremia (&gt;10 mM). Histological features include tubulo-interstitial damage reflected by inflammation, tubular atrophy and fibrosis and focal glomerulosclerosis leading to massive reduction of healthy glomeruli within the remnant population (&lt;10%). Follow-up until 12 weeks after SNX shows further progression of CKD.

A two-stage method to establish chronic kidney disease (CKD) in the Lewis rat by surgically removing 5/6th of renal mass is described. Combination of the surgical procedure, NOS-inhibition and a high-salt diet leads to a model resembling human CKD, allowing study of causal mechanisms and development of novel therapeutic interventions.

Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements ...

Apparatus for Harvesting Tissue Microcolumns

This manuscript describes the production process for a laboratory apparatus, made from off-the-shelf components, that can be used to collect microcolumns of full-thickness skin tissue. The small size of the microcolumns allows donor sites to heal quickly without causing donor site scarring, while harvesting full-thickness tissue enables the incorporation of all cellular and extracellular components of skin tissue, including those associated with deeper dermal regions and the adnexal skin structures, which have yet to be successfully reproduced using conventional tissue engineering techniques. The microcolumns can be applied directly into skin wounds to augment healing, or they can be used as the autologous cell/tissue source for other tissue engineering approaches. The harvesting needles are made by modifying standard hypodermic needles, and they can be used alone for harvesting small amounts of tissue or coupled with a simple suction-based collection system (also made from commonly available laboratory supplies) for high-volume harvesting to facilitate studies in large animal models.

Here we describe a protocol for producing harvesting needles that can be used to collect full-thickness skin tissue without causing donor site scarring. The needles can be combined with a simple collection system to achieve high-volume harvesting.

This manuscript describes the production process for a laboratory apparatus, made from off-the-shelf components, that can be used to collect microcolumns ...

Bioengineering

Second Harmonic Generation Signals in Rabbit Sclera As a Tool for Evaluation of Therapeutic Tissue Cross-linking (TXL) for Myopia

Methods to strengthen tissue by introducing chemical bonds (non-enzymatic cross-linking) into structural proteins (fibrillar collagens) for therapy include photochemical cross-linking and tissue cross-linking (TXL) methods. Such methods for inducing mechanical tissue property changes are being employed to the cornea in corneal thinning (mechanically weakened) disorders such as keratoconus as well as the sclera in progressive myopia, where thinning and weakening of the posterior sclera occurs and likely contributes to axial elongation. The primary target proteins for such tissue strengthening are fibrillar collagens which constitute the great majority of dry weight proteins in the cornea and sclera. Fortuitously, fibrillar collagens are the main source of second harmonic generation signals in the tissue extracellular space. Therefore, modifications of the collagen proteins, such as those induced through cross-linking therapies, could potentially be detected and quantitated through the use of second harmonic generation microscopy (SHGM). Monitoring SHGM signals through the use of a laser scanning microscopy system coupled with an infrared excitation light source is an exciting modern imaging method that is enjoying widespread usage in the biomedical sciences. Thus, the present study was undertaken in order to evaluate the use of SHGM microscopy as a means to measure induced cross-linking effects in ex vivo rabbit sclera, following an injection of a chemical cross-linking agent into the sub-Tenon&#39;s space (sT), an injection approach that is standard practice for causing ocular anesthesia during ophthalmologic clinical procedures. The chemical cross-linking agent, sodium hydroxymethylglycinate (SMG), is from a class of cosmetic preservatives known as formaldehyde releasing agents (FARs). Scleral changes following reaction with SMG resulted in increases in SHG signals and correlated with shifts in thermal denaturation temperature, a standard method for evaluating induced tissue cross-linking effects.

Second Harmonic Generation Signals in Rabbit Sclera As a Tool for Evaluation of Therapeutic Tissue Cross-linking TXL for Myopia

This protocol describes techniques for evaluating chemical cross-linking of the rabbit sclera using&#160;second harmonic generation imaging and differential scanning calorimetry.

Methods to strengthen tissue by introducing chemical bonds (non-enzymatic cross-linking) into structural proteins (fibrillar collagens) for therapy ...

Mechanical Micronization of Lipoaspirates for Regenerative Therapy

Stromal vascular fraction (SVF) has become a regenerative tool for various diseases; however, legislation strictly regulates the clinical application of cell products using collagenase. Here, we present a protocol to generate an injectable mixture of SVF cells and native extracellular matrix from adipose tissue by a purely mechanical process. Lipoaspirates are put into a centrifuge and spun at 1,200 x g for 3 min. The middle layer is collected and separated into two layers (high-density fat at the bottom and low-density fat on the top). The upper layer is directly emulsified by intersyringe shifting, at a rate of 20 mL/s for 6x to 8x. The emulsified fat is centrifuged at 2,000 x g for 3 min, and the sticky substance under the oil layer is collected and defined as the extracellular matrix (ECM)/SVF-gel. The oil on the top layer is collected. Approximately 5 mL of oil is added to 15 mL of high-density fat and emulsified by intersyringe shifting, at a rate of 20 mL/s for 6x to 8x. The emulsified fat is centrifuged at 2,000 x g for 3 min, and the sticky substance is also ECM/SVF-gel. After the transplantation of the ECM/SVF-gel into nude mice, the graft is harvested and assessed by histologic examination. The result shows that this product has the potential to regenerate into normal adipose tissue. This procedure is a simple, effective mechanical dissociation procedure to condense the SVF cells embedded in their natural supportive ECM for regenerative purposes.

Here, we present a protocol to obtain stromal vascular fraction from adipose tissue through a series of mechanical processes, which include emulsification and multiple centrifugations.

Stromal vascular fraction (SVF) has become a regenerative tool for various diseases; however, legislation strictly regulates the clinical application of ...

Adjunctive Diode Laser Therapy and Probiotic Lactobacillus Therapy in the Treatment of Periodontitis and Peri-Implant Disease

Periodontal and peri-implant diseases are plaque-induced infections with a high prevalence, seriously impairing people&#39;s quality of life. The diode laser has long been recommended as adjunctive therapy in treating periodontitis. However, the optimal combination of usage mode (inside or outside periodontal pocket) and application regimen (single or multiple sessions of appointment) has not been described in detail. Meanwhile, probiotic Lactobacillus is regarded as a potential adjuvant in the management of the peri-implant disease. Nonetheless, a detailed protocol for an effective probiotic application is lacking. This article aims to summarize two clinical protocols. For periodontitis, the optimal collaboration of laser usage mode and application regimen was identified. Regarding peri-implant mucositis, a combined therapy containing professional topical use and home administration of probiotic Lactobacillus was established. This updated laser protocol clarifies the relationship between the treatment mode (inside or outside the periodontal pocket) and the number of laser appointments, further refining the existing diode laser therapy. For inside pocket irradiation, a single session of laser treatment is suggested whereas, for outside pocket irradiation, multiple sessions of laser treatment provide better effects. The improved probiotic Lactobacillus therapy resulted in the disappearance of swelling of the peri-implant mucosa, a reduced bleeding on probing (BOP), and an obvious reduction and good control of plaque and pigmentation; however, probing pocket depth (PPD) had limited improvement. The current protocol should be regarded as preliminary and could be further enhanced.

Adjunctive Diode Laser Therapy and Probiotic Lactobacillus Therapy in the Treatment of Periodontitis and Peri-Implant Disease

This article describes two protocols: 1) adjunctive diode laser therapy for treating periodontitis and 2) probiotic Lactobacillus therapy for treating peri-implant disease, with emphasis on the laser usage mode (inside or outside pocket), laser application regimen (single or multiple sessions), and a probiotic protocol of professional and home administration.

Periodontal and peri-implant diseases are plaque-induced infections with a high prevalence, seriously impairing people&#39;s quality of life. The diode ...

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ

Here, we describe a protocol to induce switchable in vivo photogeneration of endogenous reactive oxygen species (ROS) in mouse skin. This transient production of ROS in situ efficiently activates cell proliferation in stem cell niches and stimulates tissue regeneration as strongly manifested through the acceleration of burn healing and hair follicle growth processes. The protocol is based on a regulatable photodynamic treatment that treats the tissue with precursors of the endogenous photosensitizer protoporphyrin IX and further irradiates the tissue with red light under tightly controlled physicochemical parameters. Overall, this protocol constitutes an interesting experimental tool to analyze ROS biology.

The aim of this protocol is to induce transient in vivo production of nonlethal levels of reactive oxygen species (ROS) in mouse skin, further promoting physiological responses in the tissue.

Here, we describe a protocol to induce switchable in vivo photogeneration of endogenous reactive oxygen species (ROS) in mouse skin. This transient ...

Biology

Enhancing Melasma Treatment with Tranexamic Acid and Microneedling Therapy

Roller Microneedle Combined with Tranexamic Acid Solution in Treating Melasma

Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective management. The precise underlying causes of melasma remain elusive, and the current therapeutic approaches predominantly encompass pharmaceutical and laser interventions, with limited efficacy. Transdermal administration stands as a prevalent treatment method for melasma, often facilitated by the application of microneedles. Among these, tranexamic acid emerges as a frequently employed therapeutic agent. A subset of microneedles, known as roller microneedles, plays a significant role in this approach by delicately puncturing the epidermis with multiple fine needles, synergizing with drug delivery. This methodology not only enhances drug absorption but also augments treatment efficacy while minimizing tissue trauma. These attributes forecast promising avenues for the treatment of melasma. This article primarily introduces the combination of roller microneedle and tranexamic acid solution in the treatment of melasma and demonstrates the efficacy of roller microneedle and tranexamic acid solution in the treatment of melasma through clinical cases.

Author Spotlight: Non-Surgical Treatment of Melasma&#8211; Microneedling with Tranexamic Acid

This article presents a protocol to conduct the treatment of melasma by using roller microneedles in combination with tranexamic acid solution and evaluate the efficacy.

Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective ...

Enhancement of Facial Rejuvenation Through a Combination of 1565 nm Non-Ablative Fractional Laser with 30% Supramolecular Salicylic Acid

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